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1. Implementation of corticosteroids in treatment of COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK: prospective, cohort study

Author: Fiina Närhi, BMedSci, S Ramani Moonesinghe, ProfMD[Res], Susan D Shenkin, PhD, Thomas M Drake, MBChB, Rachel H Mulholland, MSci, Cara Donegan, BSc, Jake Dunning, PhD, Cameron J Fairfield, MBChB, Michelle Girvan, BSc, Hayley E Hardwick, Antonia Ho, PhD, Gary Leeming, BA, Jonathan S Nguyen-Van-Tam, ProfPhD, Riinu Pius, PhD, Clark D Russell, MBChB, Catherine A Shaw, PhD, Rebecca G Spencer, LLM, Lance Turtle, PhD, Peter J M Openshaw, ProfPhD, J Kenneth Baillie, ProfPhD, Ewen M Harrison, ProfPhD, Malcolm G Semple, ProfPhD, Annemarie B Docherty, PhD, J Kenneth Baillie, Malcolm G Semple, Peter JM Openshaw, Gail Carson, Beatrice Alex, Petros Andrikopoulos, Benjamin Bach, Wendy S Barclay, Debby Bogaert, Meera Chand, Kanta Chechi, Graham S Cooke, Ana da Silva Filipe, Thushan de Silva, Annemarie B Docherty, Gon¸alo dos Santos Correia, Marc-Emmanuel Dumas, Jake Dunning, Tom Fletcher, Christopher A Green, William Greenhalf, Julian Griffin, Rishi K Gupta, Ewen M Harrison, Julian A Hiscox, Antonia YW Ho, Peter W Horby, Samreen Ijaz, Say Khoo, Paul Klenerman, Andrew Law, Matthew Lewis, Sonia Liggi, Wei Shen Lim, Lynn Maslen, Alexander J Mentzer, Laura Merson, Alison M Meynert, Shona C Moore, Mahdad Noursadeghi, Michael Olanipekun, Anthonia Osagie, Massimo Palmarini, Carlo Palmieri, William A Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L Robertson, Clark D Russell, Vanessa Sancho-Shimizu, Caroline Sands, Janet T Scott, Louise Sigfrid, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Olivia V Swann, Zoltan Takats, Panteleimon Takis, Richard S Tedder, AA Roger Thompson, Emma C Thomson, Ryan S Thwaites, Lance CW Turtle, Maria Zambon, Hayley Hardwick, Chloe Donohue, Fiona Griffiths, Wilna Oosthuyzen, Cara Donegan, Rebecca G Spencer, Lisa Norman, Riinu Pius, Thomas M Drake, Cameron J Fairfield, Stephen R Knight, Kenneth A Mclean, Derek Murphy, Catherine A Shaw, Jo Dalton, Michelle Girvan, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Sophie Halpin, Clare Jackson, Carrol Gamble, Daniel Plotkin, James Lee, Gary Leeming, Murray Wham, Sara Clohisey, Ross Hendry, James Scott-Brown, Victoria Shaw, Sarah E McDonald, Seán Keating, Katie A. Ahmed, Jane A Armstrong, Milton Ashworth, Innocent G Asiimwe, Siddharth Bakshi, Samantha L Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Benjamin WA Catterall, Jordan J Clark, Emily A Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis WS Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Rebecca L Jensen, Christopher B Jones, Trevor R Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A Livoti, Maria Mancini, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S Miah, Joanna Middleton, Joyce Mitchell, Ellen G Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E Shaw, Rebecca K Shears, Benjamin Small, Krishanthi S Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Lisa Flaherty, Nicole Maziere, Emily Cass, Alejandra Doce Carracedo, Nicola Carlucci, Anthony Holmes, Hannah Massey, Lee Murphy, Sarah McCafferty, Richard Clark, Angie Fawkes, Kirstie Morrice, Alan Maclean, Nicola Wrobel, Lorna Donelly, Audrey Coutts, Katarzyna Hafezi, Louise MacGillivray, Tammy Gilchrist, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L. Aldera, Ana Alegria, Sam Allen, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Colin Berry, Nicola Best, Pieter Bothma, David Chadwick, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic, Phil Donnison, Sam Douthwaite, Andrew Drummond, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Clive Graham, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Mariyam Mirfenderesky, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Lillian Norris, Matthew K. O'Shea, Igor Otahal, Marlies Ostermann, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Tim Planche, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Bobby Ruge, Brendan Ryan, Taranprit Saluja, Matthias Schmid, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Nick Vallotton, Rama Vancheeswaran, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Padmasayee Papineni, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Sarah Sarah, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G Wootton, Andrew Workman, Bryan Yates, and Peter Young
Subjects: Computer applications to medicine. Medical informatics, R858-859.7
Abstract: Summary: Background: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. Methods: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. Findings: Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70–0·89], p=0·0001, for 70–79 years; 0·52 [0·46–0·58], p80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75–80% in January, 2021. Interpretation: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. Funding: UK National Institute for Health Research and UK Medical Research Council.
Published: 2022
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2. Frailty and Emergency Surgery: Results of a Systematic Review and Meta-Analysis

Author: Tamas Leiner, David Nemeth, Peter Hegyi, Klementina Ocskay, Marcell Virag, Szabolcs Kiss, Mate Rottler, Matyas Vajda, Alex Varadi, and Zsolt Molnar
Subjects: frail adults, emergency surgery, mortality, Clinical Frailty Scale, meta-analysis, Medicine (General), R5-920
Abstract: BackgroundFrailty, a “syndrome of loss of reserves,” is a decade old concept. Initially it was used mainly in geriatrics but lately its use has been extended into other specialties including surgery. Our main objective was to examine the association between frailty and mortality, between frailty and length of hospital stay (LOS) and frailty and readmission within 30 days in the emergency surgical population.MethodsStudies reporting on frailty in the emergency surgical population were eligible. MEDLINE (via PubMed), EMBASE, Scopus, CENTRAL, and Web of Science were searched with terms related to acute surgery and frail*. We searched for eligible articles without any restrictions on the 2nd of November 2020. Odds ratios (OR) and weighted mean differences (WMD) were calculated with 95% confidence intervals (CI), using a random effect model. Risk of bias assessment was performed according to the recommendations of the Cochrane Collaboration. As the finally selected studies were either prospective or retrospective cohorts, the “Quality In Prognosis Studies” (QUIPS) tool was used.ResultsAt the end of the selection process 21 eligible studies with total 562.070 participants from 8 countries were included in the qualitative and the quantitative synthesis. Patients living with frailty have higher chance of dying within 30 days after an emergency surgical admission (OR: 1.99; CI: 1.76–2.21; p < 0.001). We found a tendency of increased LOS with frailty in acute surgical patients (WMD: 4.75 days; CI: 1.79–7.71; p = 0.002). Patients living with frailty have increased chance of 30-day readmission after discharge (OR: 1.36; CI: 1.06–1.75; p = 0.015).ConclusionsAlthough there is good evidence that living with frailty increases the chance of unfavorable outcomes, further research needs to be done to assess the benefits and costs of frailty screening for emergency surgical patients.Systematic Review RegistrationThe review protocol was registered on the PROSPERO International Prospective Register of Systematic Reviews (CRD42021224689).
Published: 2022
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3. The impact of viral mutations on recognition by SARS-CoV-2 specific T cells

Author: Thushan I. de Silva, Guihai Liu, Benjamin B. Lindsey, Danning Dong, Shona C. Moore, Nienyun Sharon Hsu, Dhruv Shah, Dannielle Wellington, Alexander J. Mentzer, Adrienn Angyal, Rebecca Brown, Matthew D. Parker, Zixi Ying, Xuan Yao, Lance Turtle, Susanna Dunachie, Mala K. Maini, Graham Ogg, Julian C. Knight, Yanchun Peng, Sarah L. Rowland-Jones, Tao Dong, David M. Aanensen, Khalil Abudahab, Helen Adams, Alexander Adams, Safiah Afifi, Dinesh Aggarwal, Shazaad S.Y. Ahmad, Louise Aigrain, Adela Alcolea-Medina, Nabil-Fareed Alikhan, Elias Allara, Roberto Amato, Tara Annett, Stephen Aplin, Cristina V. Ariani, Hibo Asad, Amy Ash, Paula Ashfield, Fiona Ashford, Laura Atkinson, Stephen W. Attwood, Cressida Auckland, Alp Aydin, David J. Baker, Paul Baker, Carlos E. Balcazar, Jonathan Ball, Jeffrey C. Barrett, Magdalena Barrow, Edward Barton, Matthew Bashton, Andrew R. Bassett, Rahul Batra, Chris Baxter, Nadua Bayzid, Charlotte Beaver, Angela H. Beckett, Shaun M. Beckwith, Luke Bedford, Robert Beer, Andrew Beggs, Katherine L. Bellis, Louise Berry, Beatrice Bertolusso, Angus Best, Emma Betteridge, David Bibby, Kelly Bicknell, Debbie Binns, Alec Birchley, Paul W. Bird, Chloe Bishop, Rachel Blacow, Victoria Blakey, Beth Blane, Frances Bolt, James Bonfield, Stephen Bonner, David Bonsall, Tim Boswell, Andrew Bosworth, Yann Bourgeois, Olivia Boyd, Declan T. Bradley, Cassie Breen, Catherine Bresner, Judith Breuer, Stephen Bridgett, Iraad F. Bronner, Ellena Brooks, Alice Broos, Julianne R. Brown, Giselda Bucca, Sarah L. Buchan, David Buck, Matthew Bull, Phillipa J. Burns, Shirelle Burton-Fanning, Timothy Byaruhanga, Matthew Byott, Sharon Campbell, Alessandro M. Carabelli, James S. Cargill, Matthew Carlile, Silvia F. Carvalho, Anna Casey, Anibolina Castigador, Jana Catalan, Vicki Chalker, Nicola J. Chaloner, Meera Chand, Joseph G. Chappell, Themoula Charalampous, Wendy Chatterton, Yasmin Chaudhry, Carol M. Churcher, Gemma Clark, Phillip Clarke, Benjamin J. Cogger, Kevin Cole, Jennifer Collins, Rachel Colquhoun, Thomas R. Connor, Kate F. Cook, Jason Coombes, Sally Corden, Claire Cormie, Nicholas Cortes, Marius Cotic, Seb Cotton, Simon Cottrell, Lindsay Coupland, MacGregor Cox, Alison Cox, Noel Craine, Liam Crawford, Aidan Cross, Matthew R. Crown, Dorian Crudgington, Nicola Cumley, Tanya Curran, Martin D. Curran, Ana da Silva Filipe, Gavin Dabrera, Alistair C. Darby, Rose K. Davidson, Alisha Davies, Robert M. Davies, Thomas Davis, Daniela de Angelis, Elen De Lacy, Leonardo de Oliveira Martins, Johnny Debebe, Rebecca Denton-Smith, Samir Dervisevic, Rebecca Dewar, Jayasree Dey, Joana Dias, Donald Dobie, Matthew J. Dorman, Fatima Downing, Megan Driscoll, Louis du Plessis, Nichola Duckworth, Jillian Durham, Kirstine Eastick, Lisa J. Easton, Richard Eccles, Jonathan Edgeworth, Sue Edwards, Kate El Bouzidi, Sahar Eldirdiri, Nicholas Ellaby, Scott Elliott, Gary Eltringham, Leah Ensell, Michelle J. Erkiert, Marina Escalera Zamudio, Sarah Essex, Johnathan M. Evans, Cariad Evans, William Everson, Derek J. Fairley, Karlie Fallon, Arezou Fanaie, Ben W. Farr, Christopher Fearn, Theresa Feltwell, Lynne Ferguson, Laia Fina, Flavia Flaviani, Vicki M. Fleming, Sally Forrest, Ebenezer Foster-Nyarko, Benjamin H. Foulkes, Luke Foulser, Mireille Fragakis, Dan Frampton, Sarah Francois, Christophe Fraser, Timothy M. Freeman, Helen Fryer, Marc Fuchs, William Fuller, Kavitha Gajee, Katerina Galai, Abbie Gallagher, Eileen Gallagher, Michael D. Gallagher, Marta Gallis, Amy Gaskin, Bree Gatica-Wilcox, Lily Geidelberg, Matthew Gemmell, Iliana Georgana, Ryan P. George, Laura Gifford, Lauren Gilbert, Sophia T. Girgis, Sharon Glaysher, Emily J. Goldstein, Tanya Golubchik, Andrea N. Gomes, Sónia Gonçalves, Ian G. Goodfellow, Scott Goodwin, Salman Goudarzi, Marina Gourtovaia, Clive Graham, Lee Graham, Paul R. Grant, Luke R. Green, Angie Green, Jane Greenaway, Richard Gregory, Martyn Guest, Rory N. Gunson, Ravi K. Gupta, Bernardo Gutierrez, Sam T. Haldenby, William L. Hamilton, Samantha E. Hansford, Tanzina Haque, Kathryn A. Harris, Ian Harrison, Ewan M. Harrison, Jennifer Hart, John A. Hartley, William T. Harvey, Matthew Harvey, Mohammed O. Hassan-Ibrahim, Judith Heaney, Thomas Helmer, John H. Henderson, Andrew R. Hesketh, Jessica Hey, David Heyburn, Ellen E. Higginson, Verity Hill, Jack D. Hill, Rachel A. Hilson, Ember Hilvers, Matthew T.G. Holden, Amy Hollis, Christopher W. Holmes, Nadine Holmes, Alison H. Holmes, Richard Hopes, Hailey R. Hornsby, Myra Hosmillo, Catherine Houlihan, Hannah C. Howson-Wells, Jonathan Hubb, Hannah Huckson, Warwick Hughes, Joseph Hughes, Margaret Hughes, Stephanie Hutchings, Giles Idle, Chris J. Illingworth, Robert Impey, Dianne Irish-Tavares, Miren Iturriza-Gomara, Rhys Izuagbe, Chris Jackson, Ben Jackson, Leigh M. Jackson, Kathryn A. Jackson, David K. Jackson, Aminu S. Jahun, Victoria James, Keith James, Christopher Jeanes, Aaron R. Jeffries, Sarah Jeremiah, Andrew Jermy, Michaela John, Rob Johnson, Kate Johnson, Ian Johnston, Owen Jones, Sophie Jones, Hannah Jones, Christopher R. Jones, Neil Jones, Amelia Joseph, Sarah Judges, Gemma L. Kay, Sally Kay, Jon-Paul Keatley, Alexander J. Keeley, Anita Kenyon, Leanne M. Kermack, Manjinder Khakh, Stephen P. Kidd, Maimuna Kimuli, Stuart Kirk, Christine Kitchen, Katie Kitchman, Bridget A. Knight, Cherian Koshy, Moritz U.G. Kraemer, Sara Kumziene-Summerhayes, Dominic Kwiatkowski, Angie Lackenby, Kenneth G. Laing, Temi Lampejo, Cordelia F. Langford, Deborah Lavin, Andrew I. Lawton, Jack Lee, David Lee, Stefanie V. Lensing, Steven Leonard, Lisa J. Levett, Thanh Le-Viet, Jonathan Lewis, Kevin Lewis, Jennifier Liddle, Steven Liggett, Patrick J. Lillie, Michelle M. Lister, Rich Livett, Stephanie Lo, Nicholas J. Loman, Matthew W. Loose, Stavroula F. Louka, Katie F. Loveson, Sarah Lowdon, Hannah Lowe, Helen L. Lowe, Anita O. Lucaci, Catherine Ludden, Jessica Lynch, Ronan A. Lyons, Katrina Lythgoe, Nicholas W. Machin, George MacIntyre-Cockett, Andrew Mack, Ben Macklin, Alasdair Maclean, Emily Macnaughton, Pinglawathee Madona, Mailis Maes, Laurentiu Maftei, Adhyana I.K. Mahanama, Tabitha W. Mahungu, Daniel Mair, Joshua Maksimovic, Cassandra S. Malone, Daniel Maloney, Nikos Manesis, Robin Manley, Anna Mantzouratou, Angela Marchbank, Arun Mariappan, Inigo Martincorena, Rocio T. Martinez Nunez, Alison E. Mather, Patrick Maxwell, Megan Mayhew, Tamyo Mbisa, Clare M. McCann, Shane A. McCarthy, Kathryn McCluggage, Patrick C. McClure, J.T. McCrone, Martin P. McHugh, James P. McKenna, Caoimhe McKerr, Georgina M. McManus, Claire L. McMurray, Claire McMurray, Alan McNally, Lizzie Meadows, Nathan Medd, Oliver Megram, Mirko Menegazzo, Ian Merrick, Stephen L. Michell, Michelle L. Michelsen, Mariyam Mirfenderesky, Jeremy Mirza, Julia Miskelly, Emma Moles-Garcia, Robin J. Moll, Zoltan Molnar, Irene M. Monahan, Matteo Mondani, Siddharth Mookerjee, Christopher Moore, Jonathan Moore, Nathan Moore, Catherine Moore, Helen Morcrette, Sian Morgan, Mari Morgan, Matilde Mori, Arthur Morriss, Samuel Moses, Craig Mower, Peter Muir, Afrida Mukaddas, Florence Munemo, Robert Munn, Abigail Murray, Leanne J. Murray, Darren R. Murray, Manasa Mutingwende, Richard Myers, Eleni Nastouli, Gaia Nebbia, Andrew Nelson, Charlotte Nelson, Sam Nicholls, Jenna Nichols, Roberto Nicodemi, Kyriaki Nomikou, Justin O’Grady, Sarah O'Brien, Mina Odedra, Natasha Ohemeng-Kumi, Karen Oliver, Richard J. Orton, Husam Osman, xeine O'Toole, Nicole Pacchiarini, Debra Padgett, Andrew J. Page, Emily J. Park, Naomi R. Park, Surendra Parmar, David G. Partridge, David Pascall, Amita Patel, Bindi Patel, Steve Paterson, Brendan A.I. Payne, Sharon J. Peacock, Clare Pearson, Emanuela Pelosi, Benita Percival, Jon Perkins, Malorie Perry, Malte L. Pinckert, Steven Platt, Olga Podplomyk, Manoj Pohare, Marcus Pond, Cassie F. Pope, Radoslaw Poplawski, Jessica Powell, Jennifer Poyner, Liam Prestwood, Anna Price, James R. Price, Jacqui A. Prieto, David T. Pritchard, Sophie J. Prosolek, Georgia Pugh, Monika Pusok, Oliver G. Pybus, Hannah M. Pymont, Michael A. Quail, Joshua Quick, Clara Radulescu, Jayna Raghwani, Manon Ragonnet-Cronin, Lucille Rainbow, Diana Rajan, Shavanthi Rajatileka, Newara A. Ramadan, Andrew Rambaut, John Ramble, Paul A. Randell, Paul Randell, Liz Ratcliffe, Veena Raviprakash, Mohammad Raza, Nicholas M. Redshaw, Sara Rey, Nicola Reynolds, Alex Richter, David L. Robertson, Esther Robinson, Samuel C. Robson, Fiona Rogan, Stefan Rooke, Will Rowe, Sunando Roy, Steven Rudder, Chris Ruis, Steven Rushton, Felicity Ryan, Kordo Saeed, Buddhini Samaraweera, Christine M. Sambles, Roy Sanderson, Theo Sanderson, Fei Sang, Thea Sass, Emily Scher, Garren Scott, Carol Scott, Jasveen Sehmi, Sharif Shaaban, Divya Shah, Jessica Shaw, Ekaterina Shelest, James G. Shepherd, Liz A. Sheridan, Nicola Sheriff, Lesley Shirley, John Sillitoe, Siona Silviera, David A. Simpson, Aditi Singh, Dawn Singleton, Timofey Skvortsov, Tim J. Sloan, Graciela Sluga, Ken Smith, Kim S. Smith, Perminder Smith, Darren L. Smith, Louise Smith, Colin P. Smith, Nikki Smith, Katherine L. Smollett, Luke B. Snell, Thomas Somassa, Joel Southgate, Karla Spellman, Michael H. Spencer Chapman, Lewis G. Spurgin, Moira J. Spyer, Rachael Stanley, William Stanley, Thomas D. Stanton, Igor Starinskij, Joanne Stockton, Susanne Stonehouse, Nathaniel Storey, David J. Studholme, Malur Sudhanva, Emma Swindells, Yusri Taha, Ngee Keong Tan, Julian W. Tang, Miao Tang, Ben E.W. Taylor, Joshua F. Taylor, Sarah Taylor, Ben Temperton, Kate E. Templeton, Claire Thomas, Laura Thomson, Emma C. Thomson, Alicia Thornton, Scott A.J. Thurston, John A. Todd, Rachael Tomb, Lily Tong, Gerry Tonkin-Hill, M. Estee Torok, Jaime M. Tovar-Corona, Amy Trebes, Alexander J. Trotter, Ioulia Tsatsani, Robyn Turnbull, Katherine A. Twohig, Helen Umpleby, Anthony P. Underwood, Edith E. Vamos, Tetyana I. Vasylyeva, Sreenu Vattipally, Gabrielle Vernet, Barry B. Vipond, Erik M. Volz, Sarah Walsh, Dennis Wang, Ben Warne, Joanna Warwick-Dugdale, Elizabeth Wastnedge, Joanne Watkins, Louisa K. Watson, Sheila Waugh, Hermione J. Webster, Danni Weldon, Elaine Westwick, Thomas Whalley, Helen Wheeler, Mark Whitehead, Max Whiteley, Andrew Whitwham, Claudia Wierzbicki, Nicholas J. Willford, Lesley-Anne Williams, Rebecca Williams, Cheryl Williams, Chris Williams, Charlotte A. Williams, Rachel J. Williams, Thomas Williams, Catryn Williams, Kathleen A. Williamson, Eleri Wilson-Davies, Eric Witele, Karen T. Withell, Adam A. Witney, Paige Wolverson, Nick Wong, Trudy Workman, Victoria Wright, Derek W. Wright, Tim Wyatt, Sarah Wyllie, Li Xu-McCrae, Mehmet Yavus, Geraldine Yaze, Corin A. Yeats, Gonzalo Yebra, Wen C. Yew, Gregory R. Young, Jamie Young, Alex E. Zarebski, Peijun Zhang, J. Kenneth Baillie, Malcolm G. Semple, Peter J.M. Openshaw, Gail Carson, Beatrice Alex, Petros Andrikopoulos, Benjamin Bach, Wendy S. Barclay, Debby Bogaert, Kanta Chechi, Graham S. Cooke, Annemarie B. Docherty, Gonçalo dos Santos Correia, Marc-Emmanuel Dumas, Jake Dunning, Tom Fletcher, Christopher A. Green, William Greenhalf, Julian L. Griffin, Rishi K. Gupta, Ewen M. Harrison, Julian A. Hiscox, Antonia Ying Wai Ho, Peter W. Horby, Samreen Ijaz, Saye Khoo, Paul Klenerman, Andrew Law, Matthew R. Lewis, Sonia Liggi, Wei Shen Lim, Lynn Maslen, Laura Merson, Alison M. Meynert, Mahdad Noursadeghi, Michael Olanipekun, Anthonia Osagie, Massimo Palmarini, Carlo Palmieri, William A. Paxton, Georgios Pollakis, Nicholas Price, Clark D. Russell, Vanessa Sancho-Shimizu, Caroline J. Sands, Janet T. Scott, Louise Sigfrid, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Olivia V. Swann, Zoltan Takats, Panteleimon Takis, Richard S. Tedder, A.A. Roger Thompson, Ryan S. Thwaites, Maria Zambon, Hayley Hardwick, Chloe Donohue, Fiona Griffiths, Wilna Oosthuyzen, Cara Donegan, Rebecca G. Spencer, Jo Dalton, Michelle Girvan, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Sophie Halpin, Clare Jackson, Carrol Gamble, Daniel Plotkin, James Lee, Gary Leeming, Murray Wham, Sara Clohisey, Ross Hendry, James Scott-Brown, Victoria Shaw, Sarah E. McDonald, Seán Keating, Katie A. Ahmed, Jane A. Armstrong, Milton Ashworth, Innocent G. Asiimwe, Siddharth Bakshi, Samantha L. Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Benjamin W.A. Catterall, Jordan J. Clark, Emily A. Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis W.S. Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Rebecca L. Jensen, Christopher B. Jones, Trevor R. Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A. Livoti, Maria Mancini, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S. Miah, Joanna Middleton, Joyce Mitchell, Ellen G. Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E. Shaw, Rebecca K. Shears, Benjamin Small, Krishanthi S. Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Lisa Flaherty, Nicole Maziere, Emily Cass, Alejandra Doce Carracedo, Nicola Carlucci, Anthony Holmes, Hannah Massey, Lee Murphy, Nicola Wrobel, Sarah McCafferty, Kirstie Morrice, Alan MacLean, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L. Aldera, Ana Alegria, Sam Allen, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Colin Berry, Nicola Best, Pieter Bothma, David Chadwick, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Phil Donnison, Sam Douthwaite, Andrew Drummond, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B. Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Lillian Norris, Matthew K. O'Shea, Igor Otahal, Marlies Ostermann, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Tim Planche, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Bobby Ruge, Brendan Ryan, Taranprit Saluja, Matthias L. Schmid, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Nick Vallotton, Rama Vancheeswaran, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Padmasayee Papineni, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G. Wootton, Andrew Workman, Bryan Yates, and Peter Young
Subjects: Phylogenetics, Molecular biology, Immunology, Immune response, Virology, Science
Abstract: Summary: We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.
Published: 2021
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4. Vitamin D insufficiency in COVID-19 and influenza A, and critical illness survivors: a cross-sectional study

Author: David Price, Mark Roberts, Andrew Walden, Jason Kendall, Clark D Russell, Natalie Pattison, Daniel B Hawcutt, George Koshy, Adam Finn, Ellen G Murphy, Ewen M Harrison, Maria Zambon, Michael Murphy, Tom Solomon, Carrol Gamble, Laura Marsh, Nicholas Barrett, Nigel Chee, Paul Dark, Clive Graham, Andrew Law, Richard J Mellanby, Gail Carson, Jake Dunning, Laura Merson, Ingeborg Welters, Stephen R Knight, Thomas M Drake, Tamas Szakmany, Robert Thompson, Richard Smith, Ian Handel, Kenneth A McLean, Sam Douthwaite, David Baxter, Patrick Lillie, Dougal Atkinson, Chris Dunn, James Moon, Paul Klenerman, Catherine Hartley, Mandeep Phull, Pieter Bothma, Craig Morris, Adam Wolverson, Ana Alegria, Lawrence Wilson, Susan Jain, James Limb, Vanessa Linnett, Chris Dawson, Jason Cupitt, Sam Waddy, Guy Rousseau, Andrew Burtenshaw, Devender Roberts, Samreen Ijaz, Mark Nelson, Anthony Evans, Meera Chand, Wei Shen Lim, Catherine A Shaw, Cameron J Fairfield, Timothy S Walsh, Anil Hormis, Peter W Horby, Marlies Ostermann, Tim Reynolds, Mark Lyttle, Bryan Yates, Chloe Donohue, Anil Sharma, Jenny Child, Elaine Hardy, Julian A Hiscox, Debby Bogaert, Richard Stewart, Martin Williams, Adriano G Rossi, Catherine Cosgrove, David M Griffith, William Greenhalf, Thapas Nagarajan, Saye Khoo, Annemarie B Docherty, Christopher A Green, Hayley E Hardwick, Riinu Pius, Lisa Norman, Louise Sigfrid, Sophie Halpin, Clare Jackson, J Kenneth Baillie, Malcolm G Semple, Manu Shankar-Hari, Carlo Palmieri, Lance Turtle, Stuart Hartshorn, Rishi K Gupta, Tom Fletcher, Michelle Girvan, Peter J M Openshaw, Beatrice Alex, Benjamin Bach, Wendy S Barclay, Graham S Cooke, Alexander J Mentzer, Alison M Meynert, Mahdad Noursadeghi, Shona C Moore, Massimo Palmarini, William A Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L Robertson, Vanessa Sancho-Shimizu, Janet T Scott, Shiranee Sriskandan, David Stuart, Charlotte Summers, Richard S Tedder, Emma C Thomson, Ryan S Thwaites, Lance C W Turtle, Hayley Hardwick, Wilna Oosthuyzen, Fiona Griffiths, Derek Murphy, Jo Dalton, Egle Saviciute, Stephanie Roberts, Janet Harrison, Marie Connor, Gary Leeming, Ross Hendry, Victoria Shaw, Sarah McDonald, Katie A Ahmed, Jane A Armstrong, Milton Ashworth, Innocent G Asiimwe, Siddharth Bakshi, Samantha L Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Jordan J Clark, Emily A Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Philip Dyer, Angela Elliott, Lewis W S Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Rebecca L Jensen, Christopher B Jones, Trevor R Jones, Shadia Khandaker, Katharine King, Robyn T Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Daniella Lefteri, Lauren Lett, Lucia A Livoti, Maria Mancini, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S Miah, Joanna Middleton, Joyce Mitchell, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Debby Sales, Victoria E Shaw, Rebecca K Shears, Benjamin Small, Krishanthi S Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jordan Thomas, Erwan Trochu, Eve Wilcock, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Brian Angus, Abdul Ashish, Shahedal Bari, Gavin Barlow, Stella Barnass, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Nicola Best, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Vikki Caruth, David Chadwick, Duncan Chambler, Srikanth Chukkambotla, Tom Clark, Paul Collini, Maria-Teresa Cutino-Moguel, Samir Dervisevic, Phil Donnison, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Duncan Fullerton, Sanjeev Garg, Atul Garg, Jo Godden, Arthur Goldsmith, Daniel Harvey, Peter Havalda, Maria Hobrok, Luke Hodgson, Michael Jacobs, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, Shondipon Laha, Susan Larkin, Tamas Leiner, Jeff Little, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Mariyam Mirfenderesky, Kavya Mohandas, Quen Mok, Elinoor Moore, Patrick Morgan, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Megan Nagel, Igor Otahal, Mark Pais, Selva Panchatsharam, Hassan Paraiso, Brij Patel, Justin Pepperell, Mark Peters, Stefania Pintus, Jagtur Singh Pooni, Frank Post, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Neil Richardson, Alistair Rose, Brendan Ryan, Taranprit Saluja, Aarti Shah, Prad Shanmuga, Anna Shawcross, Jeremy Sizer, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Pradeep Subudhi, Kate Tatham, Jo Thomas, Chris Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Andrew Ustianowski, Nick Vallotton, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Rachel Wake, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Meme Wijesinghe, Stephen Winchester, Martin Wiselka, Andrew Workman, Peter Young, James Scott-Brown, Will Reynolds, Jolanta Tanianis-Hughes, Chrisopher Fegan, Danai Papakonstantinou, Effrossyni Gkrania-Klotsas, Kerri Devine, Daniel G Wootton, Padmasayee Papineni, Benjamin W A Catterall, Lara Lavelle-Langham, Emily Cass, Alejandra Doce Carracedo, Lisa Flaherty, Nicole Maziere, Hannah Massey, Anthony Holmes, Nicola Carlucci, Matthew K O'Shea, Libby van Tonder, Emma A Hurst, Natalie Z Homer, Scott G Denham, Paul A Holloway, Romit J Samanta, Ana da Silva Filipe, Thushan de Silva, A A Roger Thompson, Ruth Lyons, Murray Wham, Sara Clohisey, Sara McDonald, Seán Keating, Lorna Finch, P Matthew Ridley, J Eunice Zhang, Lee Murphy, Nicola Wrobel, Sarah McCafferty, Kirstie Morrice, Alan MacLean, Erin L Aldera, Sneha Basude, Steven Laird, and Antonia Ying Wai Ho
Subjects: Medicine
Abstract: Objectives The steroid hormone vitamin D has roles in immunomodulation and bone health. Insufficiency is associated with susceptibility to respiratory infections. We report 25-hydroxy vitamin D (25(OH)D) measurements in hospitalised people with COVID-19 and influenza A and in survivors of critical illness to test the hypotheses that vitamin D insufficiency scales with illness severity and persists in survivors.Design Cross-sectional study.Setting and participants Plasma was obtained from 295 hospitalised people with COVID-19 (International Severe Acute Respiratory and emerging Infections Consortium (ISARIC)/WHO Clinical Characterization Protocol for Severe Emerging Infections UK study), 93 with influenza A (Mechanisms of Severe Acute Influenza Consortium (MOSAIC) study, during the 2009–2010 H1N1 pandemic) and 139 survivors of non-selected critical illness (prior to the COVID-19 pandemic). Total 25(OH)D was measured by liquid chromatography-tandem mass spectrometry. Free 25(OH)D was measured by ELISA in COVID-19 samples.Outcome measures Receipt of invasive mechanical ventilation (IMV) and in-hospital mortality.Results Vitamin D insufficiency (total 25(OH)D 25–50 nmol/L) and deficiency (
Published: 2021
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5. SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

Author: Felicity Liew, Shubha Talwar, Andy Cross, Brian J. Willett, Sam Scott, Nicola Logan, Matthew K. Siggins, Dawid Swieboda, Jasmin K. Sidhu, Claudia Efstathiou, Shona C. Moore, Chris Davis, Noura Mohamed, Jose Nunag, Clara King, A.A. Roger Thompson, Sarah L. Rowland-Jones, Annemarie B. Docherty, James D. Chalmers, Ling-Pei Ho, Alexander Horsley, Betty Raman, Krisnah Poinasamy, Michael Marks, Onn Min Kon, Luke Howard, Daniel G. Wootton, Susanna Dunachie, Jennifer K. Quint, Rachael A. Evans, Louise V. Wain, Sara Fontanella, Thushan I. de Silva, Antonia Ho, Ewen Harrison, J. Kenneth Baillie, Malcolm G. Semple, Christopher Brightling, Ryan S. Thwaites, Lance Turtle, Peter J.M. Openshaw, Beatrice Alex, Petros Andrikopoulos, Benjamin Bach, Wendy S. Barclay, Debby Bogaert, Meera Chand, Kanta Chechi, Graham S. Cooke, Ana da Silva Filipe, Thushan de Silva, Gonçalo dos Santos Correia, Marc-Emmanuel Dumas, Jake Dunning, Tom Fletcher, Christopher A. Green, William Greenhalf, Julian Griffin, Rishi K. Gupta, Ewen M. Harrison, Antonia Y.W. Ho, Karl Holden, Peter W. Horby, Samreen Ijaz, Say Khoo, Paul Klenerman, Andrew Law, Matthew Lewis, Sonia Liggi, Wei Shen Lim, Lynn Maslen, Alexander J. Mentzer, Laura Merson, Alison M Meynert, Mahdad Noursadeghi, Michael Olanipekun, Anthonia Osagie, Massimo Palmarini, Carlo Palmieri, William A. Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L Robertson, Clark D. Russell, Vanessa Sancho-Shimizu, Caroline Sands, Janet T. Scott, Louise Sigfrid, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Olivia V. Swann, Zoltan Takats, Panteleimon Takis, Richard S. Tedder, Emma C. Thomson, Lance C.W. Turtle, Maria Zambon, Thomas M. Drake, Cameron J. Fairfield, Stephen R. Knight, Kenneth A. Mclean, Derek Murphy, Lisa Norman, Riinu Pius, Catherine A. Shaw, Marie Connor, Jo Dalton, Carrol Gamble, Michelle Girvan, Sophie Halpin, Janet Harrison, Clare Jackson, James Lee, Laura Marsh, Daniel Plotkin, Stephanie Roberts, Egle Saviciute, Sara Clohisey, Ross Hendry, Susan Knight, Eva Lahnsteiner, Gary Leeming, Lucy Norris, James Scott-Brown, Sarah Tait, Murray Wham, Richard Clark, Audrey Coutts, Lorna Donelly, Angie Fawkes, Tammy Gilchrist, Katarzyna Hafezi, Louise MacGillivray, Alan Maclean, Sarah McCafferty, Kirstie Morrice, Lee Murphy, Nicola Wrobel, Gail Carson, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L. Aldera, Ana Alegria, Sam Allen, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Colin Berry, Nicola Best, Pieter Bothma, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, David Chadwick, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic, Phil Donnison, Sam Douthwaite, Andrew Drummond, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Clive Graham, Tassos Grammatikopoulos, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B. Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Joanne Howard, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Thapas Nagarajan, Megan Nagel, Mark Nelson, Lillian Norris, Matthew K. O'Shea, Marlies Ostermann, Igor Otahal, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Padmasayee Papineni, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Tim Planche, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Bobby Ruge, Brendan Ryan, Taranprit Saluja, Sarah Sarah, Matthias Schmid, Aarti Shah, Manu Shankar-Hari, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jagtur Singh Pooni, Jeremy Sizer, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Nick Vallotton, Rama Vancheeswaran, Rachel Vincent, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G Wootton, Andrew Workman, Bryan Yates, Peter Young, Sarah E. McDonald, Victoria Shaw, Katie A. Ahmed, Jane A. Armstrong, Milton Ashworth, Innocent G. Asiimwe, Siddharth Bakshi, Samantha L Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Nicola Carlucci, Emily Cass, Benjamin W.A. Catterall, Jordan J. Clark, Emily A. Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Alejandra Doce Carracedo, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis W.S. Fisher, Lisa Flaherty, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Anthony Holmes, Rebecca L. Jensen, Christopher B. Jones, Trevor R. Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A Livoti, Maria Mancini, Hannah Massey, Nicole Maziere, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S. Miah, Joanna Middleton, Joyce Mitchell, Ellen G Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E. Shaw, Rebecca K. Shears, Benjamin Small, Krishanthi S. Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Seán Keating, Cara Donegan, Rebecca G. Spencer, Chloe Donohue, Fiona Griffiths, Hayley Hardwick, Wilna Oosthuyzen, K. Abel, H. Adamali, D. Adeloye, O. Adeyemi, R. Adrego, L.A. Aguilar Jimenez, S. Ahmad, N. Ahmad Haider, R. Ahmed, N. Ahwireng, M. Ainsworth, B. Al-Sheklly, A. Alamoudi, M. Ali, M. Aljaroof, A.M. All, L. Allan, R.J. Allen, L. Allerton, L. Allsop, P. Almeida, D. Altmann, M. Alvarez Corral, S. Amoils, D. Anderson, C. Antoniades, G. Arbane, A. Arias, C. Armour, L. Armstrong, N. Armstrong, D. Arnold, H. Arnold, A. Ashish, A. Ashworth, M. Ashworth, S. Aslani, H. Assefa-Kebede, C. Atkin, P. Atkin, R. Aul, H. Aung, L. Austin, C. Avram, A. Ayoub, M. Babores, R. Baggott, J. Bagshaw, D. Baguley, L. Bailey, J.K. Baillie, S. Bain, M. Bakali, M. Bakau, E. Baldry, D. Baldwin, M. Baldwin, C. Ballard, A. Banerjee, B. Bang, R.E. Barker, L. Barman, S. Barratt, F. Barrett, D. Basire, N. Basu, M. Bates, A. Bates, R. Batterham, H. Baxendale, H. Bayes, M. Beadsworth, P. Beckett, M. Beggs, M. Begum, P. Beirne, D. Bell, R. Bell, K. Bennett, E. Beranova, A. Bermperi, A. Berridge, C. Berry, S. Betts, E. Bevan, K. Bhui, M. Bingham, K. Birchall, L. Bishop, K. Bisnauthsing, J. Blaikely, A. Bloss, A. Bolger, C.E. Bolton, J. Bonnington, A. Botkai, C. Bourne, M. Bourne, K. Bramham, L. Brear, G. Breen, J. Breeze, A. Briggs, E. Bright, C.E. Brightling, S. Brill, K. Brindle, L. Broad, A. Broadley, C. Brookes, M. Broome, A. Brown, J. Brown, J.S. Brown, M. Brown, V. Brown, T. Brugha, N. Brunskill, M. Buch, P. Buckley, A. Bularga, E. Bullmore, L. Burden, T. Burdett, D. Burn, G. Burns, A. Burns, J. Busby, R. Butcher, A. Butt, S. Byrne, P. Cairns, P.C. Calder, E. Calvelo, H. Carborn, B. Card, C. Carr, L. Carr, G. Carson, P. Carter, A. Casey, M. Cassar, J. Cavanagh, M. Chablani, T. Chalder, J.D. Chalmers, R.C. Chambers, F. Chan, K.M. Channon, K. Chapman, A. Charalambou, N. Chaudhuri, A. Checkley, J. Chen, Y. Cheng, L. Chetham, C. Childs, E.R. Chilvers, H. Chinoy, A. Chiribiri, K. Chong-James, G. Choudhury, N. Choudhury, P. Chowienczyk, C. Christie, M. Chrystal, D. Clark, C. Clark, J. Clarke, S. Clohisey, G. Coakley, Z. Coburn, S. Coetzee, J. Cole, C. Coleman, F. Conneh, D. Connell, B. Connolly, L. Connor, A. Cook, B. Cooper, J. Cooper, S. Cooper, D. Copeland, T. Cosier, M. Coulding, C. Coupland, E. Cox, T. Craig, P. Crisp, D. Cristiano, M.G. Crooks, A. Cross, I. Cruz, P. Cullinan, D. Cuthbertson, L. Daines, M. Dalton, P. Daly, A. Daniels, P. Dark, J. Dasgin, A. David, C. David, E. Davies, F. Davies, G. Davies, G.A. Davies, K. Davies, M.J. Davies, J. Dawson, E. Daynes, A. De Soyza, B. Deakin, A. Deans, C. Deas, J. Deery, S. Defres, A. Dell, K. Dempsey, E. Denneny, J. Dennis, A. Dewar, R. Dharmagunawardena, N. Diar-Bakerly, C. Dickens, A. Dipper, S. Diver, S.N. Diwanji, M. Dixon, R. Djukanovic, H. Dobson, S.L. Dobson, A.B. Docherty, A. Donaldson, T. Dong, N. Dormand, A. Dougherty, R. Dowling, S. Drain, K. Draxlbauer, K. Drury, P. Dulawan, A. Dunleavy, S. Dunn, C. Dupont, J. Earley, N. Easom, C. Echevarria, S. Edwards, C. Edwardson, H. El-Taweel, A. Elliott, K. Elliott, Y. Ellis, A. Elmer, O. Elneima, D. Evans, H. Evans, J. Evans, R. Evans, R.A. Evans, R.I. Evans, T. Evans, C. Evenden, L. Evison, L. Fabbri, S. Fairbairn, A. Fairman, K. Fallon, D. Faluyi, C. Favager, T. Fayzan, J. Featherstone, T. Felton, J. Finch, S. Finney, J. Finnigan, L. Finnigan, H. Fisher, S. Fletcher, R. Flockton, M. Flynn, H. Foot, D. Foote, A. Ford, D. Forton, E. Fraile, C. Francis, R. Francis, S. Francis, A. Frankel, E. Fraser, R. Free, N. French, X. Fu, J. Fuld, J. Furniss, L. Garner, N. Gautam, J.R. 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Subjects: SARS-CoV-2 variants, Mucosal immunity, Nasal antibody, SDG 3 - Good Health and Well-being, Biochemistry, Genetics and Molecular Biology(all), SARS-CoV-2 immunity, Vaccination, COVID-19, General Medicine, Convalescent, General Biochemistry, Genetics and Molecular Biology
Abstract: Data sharing statement This is an Open Access article under the CC BY 4.0 license The ISARIC4C protocol, data sharing and publication policy are available at https://isaric4c.net. ISARIC4C's Independent Data and Material Access Committee welcomes applications for access to data and materials (https://isaric4c.net). The PHOSP-COVID protocol, consent form, definition and derivation of clinical characteristics and outcomes, training materials, regulatory documents, information about requests for data access, and other relevant study materials are available online: https://phosp.org/resource/. Access to these materials can be granted by contacting phosp@leicester.ac.uk and Phospcontracts@leicester.ac.uk. All data used in this study is available within ODAP and accessible under reasonable request. Data access criteria and information about how to request access is available online: https://phosp.org/resource/. If criteria are met and a request is made, access can be gained by signing the eDRIS user agreement. Supplementary data are available online at https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(22)00584-9/fulltext#supplementaryMaterial . Copyright © 2022 The Author(s). Background: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. Methods: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. Findings: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. Interpretation: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. Funding: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript. This work is supported by the following grants: The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute for Health and Care Research (grant references: MR/V027859/1 and COV0319). ISARIC4C is supported by grants from the National Institute for Health and Care Research (award CO-CIN-01) and the Medical Research Council (grant MC_PC_19059) Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research (grant reference: C18616/A25153). Other grants which have supported this work include: the UK Coronavirus Immunology Consortium [funder reference:1257927], the Imperial Biomedical Research Centre (NIHR Imperial BRC, grant IS-BRC-1215-20013), the Health Protection Research Unit (HPRU) in Respiratory Infections at Imperial College London and NIHR HPRU in Emerging and Zoonotic Infections at University of Liverpool, both in partnership with Public Health England, [NIHR award 200907], Wellcome Trust and Department for International Development [215091/Z/18/Z], Health Data Research UK (HDR UK) [grant code: 2021.0155], Medical Research Council [grant code: MC_UU_12014/12], and NIHR Clinical Research Network for providing infrastructure support for this research. FL is supported by an MRC clinical training fellowship [award MR/W000970/1]. LPH is supported by Oxford NIHR Biomedical Research Centre. AART is supported by a BHF Intermediate Clinical Fellowship (FS/18/13/33281). SLRJ receives support from UKRI, GCRF, Rosetrees Trust, BHIVA, EDCTP, Globvac. JDC has grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Grifols, Novartis and Insmed. RAE holds a NIHR Clinician Scientist Fellowship (CS-2016-16-020). AH is currently supported by UK Research and Innovation. NIHR and NIHR Manchester BRC. BR receives support from BHF Oxford Centre of Research Excellence, NIHR Oxford BRC and MRC. SJD is funded by an NIHR Global Research Professorship [NIHR300791]. DW is supported by an NIHR Advanced Fellowship. AH has received support from MRC and the Coronavirus Immunology Consortium (MR/V028448/1). LVW has received support from UKRI, GSK/Asthma + Lung UK and NIHR for this study. MGS has received support from NIHR UK, MRC UK and Health Protection Research Unit in Emerging & Zoonotic Infections, University of Liverpool. JKB is supported by the Wellcome Trust (223164/Z/21/Z) and UKRI (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1, and MC_PC_20029). PJMO is supported by a NIHR Senior Investigator Award [award 201385]. LT is supported by the Wellcome Trust [clinical career development fellowship grant number 205228/Z/16/Z], the Centre of Excellence in Infectious Diseases Research (CEIDR) and the Alder Hey Charity.
Published: 2022
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6. SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses

Author: Wanwisa Dejnirattisai, Jiandong Huo, Daming Zhou, Jiří Zahradník, Piyada Supasa, Chang Liu, Helen M.E. Duyvesteyn, Helen M. Ginn, Alexander J. Mentzer, Aekkachai Tuekprakhon, Rungtiwa Nutalai, Beibei Wang, Aiste Dijokaite, Suman Khan, Ori Avinoam, Mohammad Bahar, Donal Skelly, Sandra Adele, Sile Ann Johnson, Ali Amini, Thomas G. Ritter, Chris Mason, Christina Dold, Daniel Pan, Sara Assadi, Adam Bellass, Nicola Omo-Dare, David Koeckerling, Amy Flaxman, Daniel Jenkin, Parvinder K. Aley, Merryn Voysey, Sue Ann Costa Clemens, Felipe Gomes Naveca, Valdinete Nascimento, Fernanda Nascimento, Cristiano Fernandes da Costa, Paola Cristina Resende, Alex Pauvolid-Correa, Marilda M. Siqueira, Vicky Baillie, Natali Serafin, Gaurav Kwatra, Kelly Da Silva, Shabir A. Madhi, Marta C. Nunes, Tariq Malik, Peter J.M. Openshaw, J. Kenneth Baillie, Malcolm G. Semple, Alain R. Townsend, Kuan-Ying A. Huang, Tiong Kit Tan, Miles W. Carroll, Paul Klenerman, Eleanor Barnes, Susanna J. Dunachie, Bede Constantinides, Hermione Webster, Derrick Crook, Andrew J. Pollard, Teresa Lambe, Neil G. Paterson, Mark A. Williams, David R. Hall, Elizabeth E. Fry, Juthathip Mongkolsapaya, Jingshan Ren, Gideon Schreiber, David I. Stuart, Gavin R. Screaton, Christopher Conlon, Alexandra S. Deeks, John Frater, Lisa Frending, Siobhan Gardiner, Anni Jämsén, Katie Jeffery, Tom Malone, Eloise Phillips, Lucy Rothwell, Lizzie Stafford, J Kenneth Baillie, Peter JM. Openshaw, Gail Carson, Beatrice Alex, Petros Andrikopoulos, Benjamin Bach, Wendy S. Barclay, Debby Bogaert, Meera Chand, Kanta Chechi, Graham S. Cooke, Ana da Silva Filipe, Thushan de Silva, Annemarie B. Docherty, Gonçalo dos Santos Correia, Marc-Emmanuel Dumas, Jake Dunning, Tom Fletcher, Christoper A. Green, William Greenhalf, Julian L. Griffin, Rishi K. Gupta, Ewen M. Harrison, Julian A. Hiscox, Antonia Ying Wai Ho, Peter W. Horby, Samreen Ijaz, Saye Khoo, Andrew Law, Matthew R. 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Schmid, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Nick Vallotton, Rama Vancheeswaran, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Padmasayee Papineni, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G. Wootton, Andrew Workman, Bryan Yates, Peter Young, National Institute for Health Research, UK Research and Innovation, UKRI MRC COVID-19 Rapid Response Call, University of Oxford, Northwestern Polytechnical University (NPU), Charles University [Prague] (CU), Division of Immunology and Inflammation, Department of Medicine, Imperial College London-Hammersmith Hospital Campus, University of Dayton, Universiteit Gent = Ghent University (UGENT), Computational & Applied Vegetation Ecology (CAVElab), Nanjing University of Science and Technology (NJUST), Weizmann Institute of Science [Rehovot, Israël], Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Imperial College London, and Apollo - University of Cambridge Repository
Subjects: variants, receptor interaction, Omicron, SARS-CoV-2, [SDV]Life Sciences [q-bio], OPTIC Consortium, Spike, vaccines, 06 Biological Sciences, Article, General Biochemistry, Genetics and Molecular Biology, RBD, ISARIC4C Consortium, 11 Medical and Health Sciences, immune evasion, Developmental Biology
Abstract: On the 24th November 2021 the sequence of a new SARS CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titres of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic as well as Alpha, Beta, Gamma, Delta are substantially reduced or fail to neutralize. Titres against Omicron are boosted by third vaccine doses and are high in cases both vaccinated and infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of a large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses, combining mutations conferring tight binding to ACE2 to unleash evolution driven by immune escape, leading to a large number of mutations in the ACE2 binding site which rebalance receptor affinity to that of early pandemic viruses., A comprehensive analysis of sera from vaccinees, convalescent patients infected previously by multiple variants and potent monoclonal antibodies from early in the COVID-19 pandemic reveals a substantial overall reduction the ability to neutralize the SARS-CoV-2 Omicron variant, which a third vaccine dose seems to ameliorate. Structural analyses of the Omicron RBD suggest a selective pressure enabling the virus bind ACE2 with increased affinity that is offset by other changes in the receptor binding motif that facilitates immune escape.
Published: 2022
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7. Characterisation of in-hospital complications associated with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol UK: a prospective, multicentre cohort study

Author: Thomas M Drake, Aya M Riad, Cameron J Fairfield, Conor Egan, Stephen R Knight, Riinu Pius, Hayley E Hardwick, Lisa Norman, Catherine A Shaw, Kenneth A McLean, A A Roger Thompson, Antonia Ho, Olivia V Swann, Michael Sullivan, Felipe Soares, Karl A Holden, Laura Merson, Daniel Plotkin, Louise Sigfrid, Thushan I de Silva, Michelle Girvan, Clare Jackson, Clark D Russell, Jake Dunning, Tom Solomon, Gail Carson, Piero Olliaro, Jonathan S Nguyen-Van-Tam, Lance Turtle, Annemarie B Docherty, Peter JM Openshaw, J Kenneth Baillie, Ewen M Harrison, Malcolm G Semple, Beatrice Alex, Benjamin Bach, Wendy S Barclay, Debby Bogaert, Meera Chand, Graham S Cooke, Ana da Silva Filipe, Tom Fletcher, Christopher A Green, Julian A Hiscox, Antonia YW Ho, Peter W Horby, Samreen Ijaz, Say Khoo, Paul Klenerman, Andrew Law, Wei Shen Lim, Alexander J Mentzer, Alison M Meynert, Mahdad Noursadeghi, Shona C Moore, Massimo Palmarini, William A Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L Robertson, Vanessa Sancho-Shimizu, Janet T Scott, Thushan de Silva, Shiranee Sriskandan, David Stuart, Charlotte Summers, Richard S Tedder, Emma C Thomson, AA Roger Thompson, Ryan S Thwaites, Lance CW Turtle, Rishi K Gupta, Carlo Palmieri, Maria Zambon, Marc-Emmanuel Dumas, Julian Griffin, Zoltan Takats, Kanta Chechi, Petros Andrikopoulos, Anthonia Osagie, Michael Olanipekun, Sonia Liggi, Matthew Lewis, Gonçalo dos Santos Correia, Caroline Sands, Panteleimon Takis, Lynn Maslen, Hayley Hardwick, Chloe Donohue, Fiona Griffiths, Wilna Oosthuyzen, Kenneth A Mclean, Derek Murphy, Jo Dalton, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Sophie Halpin, Carrol Gamble, James Lee, Gary Leeming, Murray Wham, Sara Clohisey, Ross Hendry, James Scott-Brown, William Greenhalf, Victoria Shaw, Sarah E McDonald, Seán Keating, Katie A. Ahmed, Jane A Armstrong, Milton Ashworth, Innocent G Asiimwe, Siddharth Bakshi, Samantha L Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Benjamin WA Catterall, Jordan J Clark, Emily A Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis WS Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Rebecca L Jensen, Christopher B Jones, Trevor R Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A Livoti, Maria Mancini, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S Miah, Joanna Middleton, Joyce Mitchell, Ellen G Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E Shaw, Rebecca K Shears, Benjamin Small, Krishanthi S Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Lisa Flaherty, Nicole Maziere, Emily Cass, Alejandra Doce Carracedo, Nicola Carlucci, Anthony Holmes, Hannah Massey, Lee Murphy, Nicola Wrobel, Sarah McCafferty, Kirstie Morrice, Alan MacLean, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L. Aldera, Ana Alegria, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Nicola Best, Pieter Bothma, David Chadwick, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic, Phil Donnison, Sam Douthwaite, Andrew Drummond, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Clive Graham, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Mariyam Mirfenderesky, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Lillian Norris, Matthew K. O'Shea, Igor Otahal, Marlies Ostermann, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Brendan Ryan, Taranprit Saluja, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Nick Vallotton, Rama Vancheeswaran, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Padmasayee Papineni, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Sarah Sarah, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G Wootton, Andrew Workman, Bryan Yates, Peter Young, investigators, ISARIC4C, Division of Computational and Systems Medicine, Imperial College London, London, SW7 2AZ, UK, Imperial College London - National Heart and Lung Institute, Centre National de la Recherche Scientifique (CNRS), Department of Pathology and Laboratory Medicine, University of California, National Institute for Health Research, and UKRI MRC COVID-19 Rapid Response Call
Subjects: MESH: United Kingdom, Male, Pediatrics, Respiratory Tract Diseases, MESH: Comorbidity, MESH: Hospitalization, Comorbidity, 030204 cardiovascular system & hematology, MESH: World Health Organization, MESH: Clinical Protocols, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: COVID-19, Medicine, Hospital Mortality, Prospective Studies, 030212 general & internal medicine, ISARIC4C investigators, Prospective cohort study, 11 Medical and Health Sciences, MESH: Aged, United Kingdom/epidemiology, Incidence (epidemiology), Clinical Protocols/standards, Age Factors, Articles, General Medicine, MESH: Hospitals, Hospitals, 3. Good health, Hospitalization, Cardiovascular Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cohort, COVID-19/complications, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Cohort study, medicine.medical_specialty, MEDLINE, World Health Organization, MESH: Nervous System Diseases, 03 medical and health sciences, General & Internal Medicine, Humans, MESH: SARS-CoV-2, MESH: Hospital Mortality, Survival analysis, Aged, MESH: Age Factors, MESH: Humans, SARS-CoV-2, business.industry, MESH: Cardiovascular Diseases, COVID-19, medicine.disease, MESH: Male, MESH: Prospective Studies, MESH: Respiratory Tract Diseases, Nervous System Diseases, business, Complication, MESH: Female
Abstract: BackgroundCOVID-19 is a multi-system disease and patients who survive may experience in-hospital complications. These complications are likely to have important short and long-term consequences for patients, healthcare utilisation, healthcare system preparedness, and society amidst the ongoing COVID-19 pandemic. Our aim was to characterise the extent and impact of COVID-19 complications, particularly in those who survive using the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK).MethodsA multicentre, prospective cohort study in 302 UK healthcare facilities of adults hospitalised with COVID-19 between 17th January and 4th August 2020. Complications were defined as organ specific diagnoses occurring alone or in addition to any hallmarks of COVID-19 illness. Outcomes included death, critical care use, and ability to self-care at hospital discharge. We used multilevel logistic regression and survival models to explore associations between these outcomes and in-hospital complications, age, and pre-existing comorbidities.ResultsOf patients admitted to hospital for management of COVID-19, 49.7% (36 367/73 197) experienced at least one complication. The mean age of our cohort was 71.1 years old (SD 18.7), included more males (56.0%, 41 025/73 ) with 81.0% (59 289/73 197) of patients having at least one comorbidity. Males over 60 were most likely to experience a complication (60 y and over, 54.5% [16 579/30 416] in males and 48.2% [11 707/24 288] in females; Under 60 y, 48.8% [5179/10 609] in males, 36.6% [2814/7689] in females). Renal (24.3%, 17 752/73 197), complex respiratory 18.4% (13 486/73 197), and systemic (16.3%, 11 895/73 197) complications were most frequent. Cardiovascular (12.3%, 8973/73 197), neurological (4.3%, 3115/73 197), and gastrointestinal/liver (0.8%, 7901/73 197) complications were also reported. The presence of any complication was associated with significantly worse survival (adjusted HR 1.74, 95% CI 1.64 to 1.84) and increased admission to critical care (adjusted OR 7.25, 95% CI 6.83 to 7.69). Reduced ability to self-care at discharge was significantly greater in patients who experienced a complication (adjusted OR 2.42, 95% CI 2.31 to 2.54) and was greatest in those who experienced neurological complications (adjusted OR 4.39, 95% CI 3.95 to 4.89). ConclusionsComplications and worse functional outcomes in patients admitted to hospital with COVID-19 are high, even in young, previously healthy individuals. Acute complications are associated with reduced ability to self-care at discharge, with neurological complications being associated with the worst functional outcomes. COVID-19 complications are likely to cause significant strain on health and social care in the coming years. These data will help in the design and provision of services aimed at the post-hospitalisation care of patients with COVID-19.
Published: 2021
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8. Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: a multicentre, prospective cohort study

Author: Clark D Russell, Cameron J Fairfield, Thomas M Drake, Lance Turtle, R Andrew Seaton, Dan G Wootton, Louise Sigfrid, Ewen M Harrison, Annemarie B Docherty, Thushan I de Silva, Conor Egan, Riinu Pius, Hayley E Hardwick, Laura Merson, Michelle Girvan, Jake Dunning, Jonathan S Nguyen-Van-Tam, Peter J M Openshaw, J Kenneth Baillie, Malcolm G Semple, Antonia Ho, Peter JM Openshaw, Gail Carson, Beatrice Alex, Benjamin Bach, Wendy S Barclay, Debby Bogaert, Meera Chand, Graham S Cooke, Ana da Silva Filipe, Tom Fletcher, Christopher A Green, Julian A Hiscox, Antonia YW Ho, Peter W Horby, Samreen Ijaz, Say Khoo, Paul Klenerman, Andrew Law, Wei Shen Lim, Alexander J Mentzer, Alison M Meynert, Mahdad Noursadeghi, Shona C Moore, Massimo Palmarini, William A Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L Robertson, Vanessa Sancho-Shimizu, Janet T Scott, Thushan de Silva, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Richard S Tedder, Emma C Thomson, AA Roger Thompson, Ryan S Thwaites, Lance CW Turtle, Rishi K Gupta, Carlo Palmieri, Maria Zambon, Hayley Hardwick, Chloe Donohue, Ruth Lyons, Fiona Griffiths, Wilna Oosthuyzen, Lisa Norman, Stephen R Knight, Kenneth A Mclean, Derek Murphy, Catherine A Shaw, Jo Dalton, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Sophie Halpin, Clare Jackson, Carrol Gamble, Gary Leeming, Murray Wham, Sara Clohisey, Ross Hendry, James Scott-Brown, William Greenhalf, Victoria Shaw, Sarah E McDonald, Seán Keating, Katie A. Ahmed, Jane A Armstrong, Milton Ashworth, Innocent G Asiimwe, Siddharth Bakshi, Samantha L Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Benjamin WA Catterall, Jordan J Clark, Emily A Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis WS Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Rebecca L Jensen, Christopher B Jones, Trevor R Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A Livoti, Maria Mancini, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S Miah, Joanna Middleton, Joyce Mitchell, Ellen G Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E Shaw, Rebecca K Shears, Benjamin Small, Krishanthi S Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Lisa Flaherty, Nicole Maziere, Emily Cass, Alejandra Doce Carracedo, Nicola Carlucci, Anthony Holmes, Hannah Massey, Lee Murphy, Nicola Wrobel, Sarah McCafferty, Kirstie Morrice, Alan MacLean, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L. Aldera, Ana Alegria, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Nicola Best, Pieter Bothma, David Chadwick, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic, Phil Donnison, Sam Douthwaite, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Clive Graham, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Mariyam Mirfenderesky, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Matthew K. O'Shea, Igor Otahal, Marlies Ostermann, Mark Pais, Selva Panchatsharam, Danai Papakonstantino, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Brendan Ryan, Taranprit Saluja, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Andrew Ustianowski, Nick Vallotton, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Padmasayee Papineni, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Sarah Sarah, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G Wootton, Andrew Workman, Bryan Yates, Peter Young, UK Research and Innovation, and UKRI MRC COVID-19 Rapid Response Call
Subjects: Microbiology (medical), BACTERIAL, medicine.medical_specialty, Secondary infection, Psychological intervention, World Health Organization, medicine.disease_cause, Microbiology, Haemophilus influenzae, Virology, Internal medicine, Pandemic, medicine, Humans, Prospective Studies, ISARIC4C investigators, Prospective cohort study, Pandemics, Case report form, Science & Technology, Coinfection, Diagnostic Tests, Routine, business.industry, STEWARDSHIP, COVID-19, Articles, Bacterial Infections, ADULTS, Antimicrobial, United Kingdom, Anti-Bacterial Agents, Infectious Diseases, Staphylococcus aureus, business, Life Sciences & Biomedicine
Abstract: Background: Microbiological characterisation of co-infections and secondary infections in patients with COVID-19 is lacking, and antimicrobial use is high. We aimed to describe microbiologically confirmed co-infections and secondary infections, and antimicrobial use, in patients admitted to hospital with COVID-19. Methods: The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study is an ongoing, prospective cohort study recruiting inpatients from 260 hospitals in England, Scotland, and Wales, conducted by the ISARIC Coronavirus Clinical Characterisation Consortium. Patients with a confirmed or clinician-defined high likelihood of SARS-CoV-2 infection were eligible for inclusion in the ISARIC WHO CCP-UK study. For this specific study, we excluded patients with a recorded negative SARS-CoV-2 test result and those without a recorded outcome at 28 days after admission. Demographic, clinical, laboratory, therapeutic, and outcome data were collected using a prespecified case report form. Organisms considered clinically insignificant were excluded. Findings: We analysed data from 48 902 patients admitted to hospital between Feb 6 and June 8, 2020. The median patient age was 74 years (IQR 59–84) and 20 786 (42·6%) of 48 765 patients were female. Microbiological investigations were recorded for 8649 (17·7%) of 48 902 patients, with clinically significant COVID-19-related respiratory or bloodstream culture results recorded for 1107 patients. 762 (70·6%) of 1080 infections were secondary, occurring more than 2 days after hospital admission. Staphylococcus aureus and Haemophilus influenzae were the most common pathogens causing respiratory co-infections (diagnosed ≤2 days after admission), with Enterobacteriaceae and S aureus most common in secondary respiratory infections. Bloodstream infections were most frequently caused by Escherichia coli and S aureus. Among patients with available data, 13 390 (37·0%) of 36 145 had received antimicrobials in the community for this illness episode before hospital admission and 39 258 (85·2%) of 46 061 patients with inpatient antimicrobial data received one or more antimicrobials at some point during their admission (highest for patients in critical care). We identified frequent use of broad-spectrum agents and use of carbapenems rather than carbapenem-sparing alternatives. Interpretation: In patients admitted to hospital with COVID-19, microbiologically confirmed bacterial infections are rare, and more likely to be secondary infections. Gram-negative organisms and S aureus are the predominant pathogens. The frequency and nature of antimicrobial use are concerning, but tractable targets for stewardship interventions exist. Funding: National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, UK Department for International Development, Bill & Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, and NIHR HPRU in Respiratory Infections at Imperial College London.
Published: 2021
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9. Changes in in-hospital mortality in the first wave of COVID-19: a multicentre prospective observational cohort study using the WHO Clinical Characterisation Protocol UK

Author: Annemarie B Docherty, Rachel H Mulholland, Nazir I Lone, Christopher P Cheyne, Daniela De Angelis, Karla Diaz-Ordaz, Cara Donegan, Thomas M Drake, Jake Dunning, Sebastian Funk, Marta García-Fiñana, Michelle Girvan, Hayley E Hardwick, Janet Harrison, Antonia Ho, David M Hughes, Ruth H Keogh, Peter D Kirwan, Gary Leeming, Jonathan S Nguyen Van-Tam, Riinu Pius, Clark D Russell, Rebecca G Spencer, Brian DM Tom, Lance Turtle, Peter JM Openshaw, J Kenneth Baillie, Ewen M Harrison, Malcolm G Semple, Gail Carson, Beatrice Alex, Benjamin Bach, Wendy S Barclay, Debby Bogaert, Meera Chand, Graham S Cooke, Ana da Silva Filipe, Tom Fletcher, Christopher A Green, Julian A Hiscox, Antonia YW Ho, Peter W Horby, Samreen Ijaz, Say Khoo, Paul Klenerman, Andrew Law, Wei Shen Lim, Alexander J Mentzer, Laura Merson, Alison M Meynert, Mahdad Noursadeghi, Shona C Moore, Massimo Palmarini, William A Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L Robertson, Vanessa Sancho-Shimizu, Janet T Scott, Thushan de Silva, Louise Sigfrid, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Richard S Tedder, Emma C Thomson, AA Roger Thompson, Ryan S Thwaites, Lance CW Turtle, Rishi K Gupta, Carlo Palmieri, Maria Zambon, Hayley Hardwick, Chloe Donohue, Ruth Lyons, Fiona Griffiths, Wilna Oosthuyzen, Lisa Norman, Cameron J Fairfield, Stephen R Knight, Kenneth A Mclean, Derek Murphy, Catherine A Shaw, Jo Dalton, Egle Saviciute, Stephanie Roberts, Laura Marsh, Marie Connor, Sophie Halpin, Clare Jackson, Carrol Gamble, Murray Wham, Sara Clohisey, Ross Hendry, James Scott-Brown, William Greenhalf, Victoria Shaw, Sarah E McDonald, Seán Keating, Katie A Ahmed, Jane A Armstrong, Milton Ashworth, Innocent G Asiimwe, Siddharth Bakshi, Samantha L Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Benjamin WA Catterall, Jordan J Clark, Emily A Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis WS Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Rebecca L Jensen, Christopher B Jones, Trevor R Jones, Shadia Khandaker, Katharine King, Robyn T Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A Livoti, Maria Mancini, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S Miah, Joanna Middleton, Joyce Mitchell, Ellen G Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E Shaw, Rebecca K Shears, Benjamin Small, Krishanthi S Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Lisa Flaherty, Nicole Maziere, Emily Cass, Alejandra Doce Carracedo, Nicola Carlucci, Anthony Holmes, Hannah Massey, Lee Murphy, Nicola Wrobel, Sarah McCafferty, Kirstie Morrice, Alan MacLean, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L Aldera, Ana Alegria, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Nicola Best, Pieter Bothma, David Chadwick, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic, Phil Donnison, Sam Douthwaite, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Clive Graham, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Mariyam Mirfenderesky, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Matthew K O'Shea, Igor Otahal, Marlies Ostermann, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Brendan Ryan, Taranprit Saluja, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Andrew Ustianowski, Nick Vallotton, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Padmasayee Papineni, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Sarah Sarah, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G Wooton, Andrew Workman, Bryan Yates, Peter Young, Kirwan, Peter D [0000-0001-6904-0500], Apollo - University of Cambridge Repository, Imperial College Healthcare NHS Trust- BRC Funding, GlaxoSmithKline Biologicals, National Institute for Health Research, UKRI MRC COVID-19 Rapid Response Call, and UK Research and Innovation
Subjects: Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, World Health Organization, 1117 Public Health and Health Services, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Clinical Protocols, Internal medicine, Severity of illness, Pandemic, Risk of mortality, medicine, Humans, 030212 general & internal medicine, Hospital Mortality, Prospective Studies, Prospective cohort study, ISARIC4C Investigators, Aged, COVID-19/epidemiology, Aged, 80 and over, business.industry, United Kingdom/epidemiology, Mortality rate, Confounding, COVID-19, 1103 Clinical Sciences, Odds ratio, Articles, Middle Aged, United Kingdom, 030228 respiratory system, Female, business, Cohort study, 1199 Other Medical and Health Sciences
Abstract: Background\ud \ud Mortality rates in hospitalised patients with COVID-19 in the UK appeared to decline during the first wave of the pandemic. We aimed to quantify potential drivers of this change and identify groups of patients who remain at high risk of dying in hospital.\ud \ud \ud Methods\ud \ud In this multicentre prospective observational cohort study, the International Severe Acute Respiratory and Emerging Infections Consortium WHO Clinical Characterisation Protocol UK recruited a prospective cohort of patients with COVID-19 admitted to 247 acute hospitals in England, Scotland, and Wales during the first wave of the pandemic (between March 9 and Aug 2, 2020). We included all patients aged 18 years and older with clinical signs and symptoms of COVID-19 or confirmed COVID-19 (by RT-PCR test) from assumed community-acquired infection. We did a three-way decomposition mediation analysis using natural effects models to explore associations between week of admission and in-hospital mortality, adjusting for confounders (demographics, comorbidities, and severity of illness) and quantifying potential mediators (level of respiratory support and steroid treatment). The primary outcome was weekly in-hospital mortality at 28 days, defined as the proportion of patients who had died within 28 days of admission of all patients admitted in the observed week, and it was assessed in all patients with an outcome. This study is registered with the ISRCTN Registry, ISRCTN66726260.\ud \ud \ud Findings\ud \ud Between March 9, and Aug 2, 2020, we recruited 80 713 patients, of whom 63 972 were eligible and included in the study. Unadjusted weekly in-hospital mortality declined from 32·3% (95% CI 31·8–32·7) in March 9 to April 26, 2020, to 16·4% (15·0–17·8) in June 15 to Aug 2, 2020. Reductions in mortality were observed in all age groups, in all ethnic groups, for both sexes, and in patients with and without comorbidities. After adjustment, there was a 32% reduction in the risk of mortality per 7-week period (odds ratio [OR] 0·68 [95% CI 0·65–0·71]). The higher proportions of patients with severe disease and comorbidities earlier in the first wave (March and April) than in June and July accounted for 10·2% of this reduction. The use of respiratory support changed during the first wave, with gradually increased use of non-invasive ventilation over the first wave. Changes in respiratory support and use of steroids accounted for 22·2%, OR 0·95 (0·94–0·95) of the reduction in in-hospital mortality.\ud \ud \ud Interpretation\ud \ud The reduction in in-hospital mortality in patients with COVID-19 during the first wave in the UK was partly accounted for by changes in the case-mix and illness severity. A significant reduction in in-hospital mortality was associated with differences in respiratory support and critical care use, which could partly reflect accrual of clinical knowledge. The remaining improvement in in-hospital mortality is not explained by these factors, and could be associated with changes in community behaviour, inoculum dose, and hospital capacity strain.\ud \ud \ud Funding\ud \ud National Institute for Health Research and the Medical Research Council.
Published: 2021
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10. Risk of adverse outcomes in patients with underlying respiratory conditions admitted to hospital with COVID-19 a national, multicentre prospective cohort study using the ISARIC WHO Clinical Characterisation Protocol UK

Author: Chloe I Bloom, Thomas M Drake, Annemarie B Docherty, Brian J Lipworth, Sebastian L Johnston, Jonathan S Nguyen-Van-Tam, Gail Carson, Jake Dunning, Ewen M Harrison, J Kenneth Baillie, Malcolm G Semple, Paul Cullinan, Peter J M Openshaw, Beatrice Alex, Benjamin Bach, Wendy S Barclay, Debby Bogaert, Meera Chand, Graham S Cooke, Ana da Filipe, Tom Fletcher, Christoper A Green, Julian A Hiscox, Antonia Ying Ho, Peter W Horby, Samreen Ijaz, Saye Khoo, Paul Klenerman, Andrew Law, Wei Shen Lim, Alexander J Mentzer, Laura Merson, Alison M Meynert, Mahdad Noursadeghi, Shona C Moore, Massimo Palmarini, William A Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L Robertson, Clark D Russell, Vanessa Sancho-Shimizu, Janet T Scott, Thushan de Silva, Louise Sigfrid, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Richard S Tedder, Emma C Thomson, AA Roger Thompson, Ryan S Thwaites, Lance CW Turtle, Maria Zambon, Hayley Hardwick, Chloe Donohue, Ruth Lyons, Fiona Griffiths, Wilna Oosthuyzen, Lisa Norman, Riinu Pius, Cameron J Fairfield, Stephen R Knight, Kenneth A Mclean, Derek Murphy, Catherine A Shaw, Jo Dalton, Michelle Girvan, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Sophie Halpin, Clare Jackson, Carrol Gamble, Gary Leeming, Murray Wham, Sara Clohisey, Ross Hendry, James Scott-Brown, William Greenhalf, Victoria Shaw, Sara McDonald, Seán Keating, Katie A. Ahmed, Jane A Armstrong, Milton Ashworth, Innocent G Asiimwe, Siddharth Bakshi, Samantha L Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Benjamin WA Catterall, Jordan J Clark, Emily A Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis WS Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Rebecca L Jensen, Christopher B Jones, Trevor R Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A Livoti, Maria Mancini, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S Miah, Joanna Middleton, Joyce Mitchell, Ellen G Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E Shaw, Rebecca K Shears, Benjamin Small, Krishanthi S Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Lisa Flaherty, Nicole Maziere, Emily Cass, Alejandra Doce Carracedo, Nicola Carlucci, Anthony Holmes, Hannah Massey, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Ana Alegria, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Nicola Best, Pieter Bothma, David Brealey, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, David Chadwick, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic, Phil Donnison, Sam Douthwaite, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Clive Graham, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Mariyam Mirfenderesky, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Igor Otahal, Mark Pais, Selva Panchatsharam, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Pooni, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Brendan Ryan, Taranprit Saluja, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Andrew Ustianowski, Nick Vallotton, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Sarah Wilson, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G Wooton, Andrew Workman, Bryan Yates, Peter Young, National Institute for Health Research, UK Research and Innovation, GlaxoSmithKline Biologicals, UKRI MRC COVID-19 Rapid Response Call, and Medical Research Council (MRC)
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Adolescent, Pulmonary Disease, Chronic Obstructive/complications, Respiratory System, INHALED CORTICOSTEROIDS, World Health Organization, Risk Assessment, 1117 Public Health and Health Services, Cohort Studies, Pulmonary Disease, Chronic Obstructive, Young Adult, Critical Care Medicine, Clinical Protocols, General & Internal Medicine, Internal medicine, medicine, Humans, Hospital Mortality, Prospective Studies, Young adult, Prospective cohort study, Asthma, Science & Technology, business.industry, Public health, ISARIC investigators, Respiratory disease, Asthma/complications, COVID-19, 1103 Clinical Sciences, Odds ratio, Articles, Middle Aged, medicine.disease, United Kingdom, PREVALENCE, Hospitalization, COVID-19/complications, Female, Risk assessment, business, Life Sciences & Biomedicine, Cohort study, 1199 Other Medical and Health Sciences
Abstract: BACKGROUND: Studies of patients admitted to hospital with COVID-19 have found varying mortality outcomes associated with underlying respiratory conditions and inhaled corticosteroid use. Using data from a national, multicentre, prospective cohort, we aimed to characterise people with COVID-19 admitted to hospital with underlying respiratory disease, assess the level of care received, measure in-hospital mortality, and examine the effect of inhaled corticosteroid use. METHODS: We analysed data from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study. All patients admitted to hospital with COVID-19 across England, Scotland, and Wales between Jan 17 and Aug 3, 2020, were eligible for inclusion in this analysis. Patients with asthma, chronic pulmonary disease, or both, were identified and stratified by age ( FINDINGS: 75 463 patients from 258 participating health-care facilities were included in this analysis: 860 patients younger than 16 years (74 [8·6%] with asthma), 8950 patients aged 16-49 years (1867 [20·9%] with asthma), and 65 653 patients aged 50 years and older (5918 [9·0%] with asthma, 10 266 [15·6%] with chronic pulmonary disease, and 2071 [3·2%] with both asthma and chronic pulmonary disease). Patients with asthma were significantly more likely than those without asthma to receive critical care (patients aged 16-49 years: adjusted odds ratio [OR] 1·20 [95% CI 1·05-1·37]; p=0·0080; patients aged ≥50 years: adjusted OR 1·17 [1·08-1·27]; p INTERPRETATION: Underlying respiratory conditions are common in patients admitted to hospital with COVID-19. Regardless of the severity of symptoms at admission and comorbidities, patients with asthma were more likely, and those with chronic pulmonary disease less likely, to receive critical care than patients without an underlying respiratory condition. In patients aged 16 years and older, severe asthma was associated with increased mortality compared to non-severe asthma. In patients aged 50 years and older, inhaled corticosteroid use in those with asthma was associated with lower mortality than in patients without an underlying respiratory condition; patients with chronic pulmonary disease had significantly increased mortality compared to those with no underlying respiratory condition, regardless of inhaled corticosteroid use. Our results suggest that the use of inhaled corticosteroids, within 2 weeks of admission, improves survival for patients aged 50 years and older with asthma, but not for those with chronic pulmonary disease. FUNDING: National Institute for Health Research, Medical Research Council, NIHR Health Protection Research Units in Emerging and Zoonotic Infections at the University of Liverpool and in Respiratory Infections at Imperial College London in partnership with Public Health England.
Published: 2021
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11. Non-steroidal anti-inflammatory drug use and outcomes of COVID-19 in the ISARIC Clinical Characterisation Protocol UK cohort: a matched, prospective cohort study

Author: Thomas M Drake, Cameron J Fairfield, Riinu Pius, Stephen R Knight, Lisa Norman, Michelle Girvan, Hayley E Hardwick, Annemarie B Docherty, Ryan S Thwaites, Peter J M Openshaw, J Kenneth Baillie, Ewen M Harrison, Malcolm G Semple, Peter JM Openshaw, Gail Carson, Beatrice Alex, Benjamin Bach, Wendy S Barclay, Debby Bogaert, Meera Chand, Graham S Cooke, Ana da Silva Filipe, Thushan de Silva, Jake Dunning, Tom Fletcher, Christopher A Green, Julian A Hiscox, Antonia YW Ho, Peter W Horby, Samreen Ijaz, Say Khoo, Paul Klenerman, Andrew Law, Wei Shen Lim, Alexander J Mentzer, Laura Merson, Alison M Meynert, Shona C Moore, Mahdad Noursadeghi, Massimo Palmarini, William A Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L Robertson, Clark D Russell, Vanessa Sancho-Shimizu, Janet T Scott, Louise Sigfrid, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Richard S Tedder, AA Roger Thompson, Emma C Thomson, Lance CW Turtle, Maria Zambon, Chloe Donohue, Fiona Griffiths, Hayley Hardwick, Ruth Lyons, Wilna Oosthuyzen, Kenneth A Mclean, Derek Murphy, Catherine A Shaw, Marie Connor, Jo Dalton, Carrol Gamble, Sophie Halpin, Janet Harrison, Clare Jackson, Laura Marsh, Stephanie Roberts, Egle Saviciute, Sara Clohisey, Ross Hendry, Gary Leeming, James Scott-Brown, Murray Wham, William Greenhalf, Sara McDonald, Victoria Shaw, Seán Keating, Katie A. Ahmed, Jane A Armstrong, Milton Ashworth, Innocent G Asiimwe, Siddharth Bakshi, Samantha L Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Nicola Carlucci, Emily Cass, Benjamin WA Catterall, Jordan J Clark, Emily A Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Alejandra Doce Carracedo, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis WS Fisher, Lisa Flaherty, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Anthony Holmes, Rebecca L Jensen, Christopher B Jones, Trevor R Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A Livoti, Maria Mancini, Hannah Massey, Nicole Maziere, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S Miah, Joanna Middleton, Joyce Mitchell, Ellen G Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E Shaw, Rebecca K Shears, Benjamin Small, Krishanthi S Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Alan MacLean, Sarah McCafferty, Kirstie Morrice, Lee Murphy, Nicola Wrobel, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L. Aldera, Ana Alegria, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Nicola Best, Pieter Bothma, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, David Chadwick, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic, Phil Donnison, Sam Douthwaite, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Clive Graham, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Mariyam Mirfenderesky, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Thapas Nagarajan, Megan Nagel, Mark Nelson, Matthew K. O'Shea, Marlies Ostermann, Igor Otahal, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Padmasayee Papineni, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Brendan Ryan, Taranprit Saluja, Sarah Sarah, Aarti Shah, Manu Shankar-Hari, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jagtur Singh Pooni, Jeremy Sizer, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Andrew Ustianowski, Nick Vallotton, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G Wooton, Andrew Workman, Bryan Yates, Peter Young, investigators, ISARIC4C, Horby, PW, UKRI MRC COVID-19 Rapid Response Call, National Institute for Health Research, Medical Research Council (MRC), and UK Research and Innovation
Subjects: medicine.medical_specialty, business.industry, Immunology, Acute kidney injury, Articles, medicine.disease, Logistic regression, Rheumatology, Internal medicine, Cohort, Propensity score matching, Epidemiology, medicine, Immunology and Allergy, Medical prescription, business, Prospective cohort study, ISARIC4C Investigators, Cohort study
Abstract: Background Early in the pandemic it was suggested that pre-existing use of non-steroidal anti-inflammatory drugs (NSAIDs) could lead to increased disease severity in patients with COVID-19. NSAIDs are an important analgesic, particularly in those with rheumatological disease, and are widely available to the general public without prescription. Evidence from community studies, administrative data, and small studies of hospitalised patients suggest NSAIDs are not associated with poorer COVID-19 outcomes. We aimed to characterise the safety of NSAIDs and identify whether pre-existing NSAID use was associated with increased severity of COVID-19 disease. Methods This prospective, multicentre cohort study included patients of any age admitted to hospital with a confirmed or highly suspected SARS-CoV-2 infection leading to COVID-19 between Jan 17 and Aug 10, 2020. The primary outcome was in-hospital mortality, and secondary outcomes were disease severity at presentation, admission to critical care, receipt of invasive ventilation, receipt of non-invasive ventilation, use of supplementary oxygen, and acute kidney injury. NSAID use was required to be within the 2 weeks before hospital admission. We used logistic regression to estimate the effects of NSAIDs and adjust for confounding variables. We used propensity score matching to further estimate effects of NSAIDS while accounting for covariate differences in populations. Results Between Jan 17 and Aug 10, 2020, we enrolled 78 674 patients across 255 health-care facilities in England, Scotland, and Wales. 72 179 patients had death outcomes available for matching; 40 406 (56·2%) of 71 915 were men, 31 509 (43·8%) were women. In this cohort, 4211 (5·8%) patients were recorded as taking systemic NSAIDs before admission to hospital. Following propensity score matching, balanced groups of NSAIDs users and NSAIDs non-users were obtained (4205 patients in each group). At hospital admission, we observed no significant differences in severity between exposure groups. After adjusting for explanatory variables, NSAID use was not associated with worse in-hospital mortality (matched OR 0·95, 95% CI 0·84–1·07; p=0·35), critical care admission (1·01, 0·87–1·17; p=0·89), requirement for invasive ventilation (0·96, 0·80–1·17; p=0·69), requirement for non-invasive ventilation (1·12, 0·96–1·32; p=0·14), requirement for oxygen (1·00, 0·89–1·12; p=0·97), or occurrence of acute kidney injury (1·08, 0·92–1·26; p=0·33). Interpretation NSAID use is not associated with higher mortality or increased severity of COVID-19. Policy makers should consider reviewing issued advice around NSAID prescribing and COVID-19 severity. Funding National Institute for Health Research and Medical Research Council.
Published: 2021
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12. Clinical Frailty Scale (CFS) Indicated Frailty is Associated with Increased In-Hospital and 30-Day Mortality in COVID-19 Patients: A Systematic Review and Meta-Analysis

Author: Tamas Leiner, Péter Hegyi, Máté Rottler, Bálint Erőss, Tihamer Molnar, Anikó Görbe, Zsolt Molnár, Klementina Ocskay, and Marcell Virág
Subjects: Gerontology, Coronavirus disease 2019 (COVID-19), Scale (ratio), business.industry, 30 day mortality, Meta-analysis, Medicine, business, human activities
Abstract: Background: The concept of frailty provides an age-independent, easy-to-use tool for risk stratification. We aimed to summarize the evidence regarding the use of frailty tools in COVID-19, assessing the risk of frail patients for in-hospital and 30-day mortality, intensive care unit (ICU) admission, and length of hospitalization (LOH).Methods: The protocol was prospectively registered via PROSPERO (CRD42021241544). Studies reporting on frailty in COVID-19 patients were eligible. We compared in-hospital and 30-day mortality, lengths of stay and ICU admission in frail and non-frail COVID-19 patients. We also compared average frailty in COVID-19 survivors and non-survivors. MEDLINE (via PubMed), EMBASE, Scopus, CENTRAL, and Web of Science were searched up to 3 February 2021 with terms related to COVID-19 and frail*. Search, selection, data extraction and risk of bias assessment were conducted in duplicate by two independent review authors. The QUIPS tool was used for the risk of bias assessment. Odds ratios (OR) and weighted mean differences (WMD) were calculated with 95% confidence intervals (CI) using a random effect model. Heterogeneity was assessed using the I2 and χ2 tests.Results: From 1693 records identified, 27 were included in the qualitative and 21 in the quantitative synthesis. Clinical Frailty Scale (CFS) was used in 24 studies, the Hospital Frailty Risk Score (HFRS) by one and the Frail Non-Disabled questionnaire by another one. One study reported both CFS and HFRS. We found that frail patients (CFS 5–9) compared to non-frail patients (CFS 1–4) have a higher risk for both in-hospital (OR: 2.77; CI: 1.86–4.15) and 30-day mortality (OR: 1.47; CI:1.05–2.06). Frail patients (CFS 5–9) were less likely to be admitted to ICU (OR 0.05, CI: 0.01–0.16). Statistical heterogeneity was not present for CFS 5–9 30-day mortality OR and ICU admission OR (CFS 1–3 vs 4–9), and was moderate for in-hospital mortality WMD. Quantitative synthesis for LOH was not feasible. Most studies carried a high risk of bias.Conclusions: As determined by CFS, frailty is strongly associated with in-hospital and 30-day mortality; hence, investigating its use in deciding on ICU admission further in COVID-19 is warranted.
Published: 2021
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13. Development and validation of the ISARIC 4C deterioration model for adults hospitalised with COVID-19: a prospective cohort study

Author: Rishi K Gupta, Ewen M Harrison, Antonia Ho, Annemarie B Docherty, Stephen R Knight, Maarten van Smeden, Ibrahim Abubakar, Marc Lipman, Matteo Quartagno, Riinu Pius, Iain Buchan, Gail Carson, Thomas M Drake, Jake Dunning, Cameron J Fairfield, Carrol Gamble, Christopher A Green, Sophie Halpin, Hayley E Hardwick, Karl A Holden, Peter W Horby, Clare Jackson, Kenneth A Mclean, Laura Merson, Jonathan S Nguyen-Van-Tam, Lisa Norman, Piero L Olliaro, Mark G Pritchard, Clark D Russell, James Scott-Brown, Catherine A Shaw, Aziz Sheikh, Tom Solomon, Cathie Sudlow, Olivia V Swann, Lance Turtle, Peter J M Openshaw, J Kenneth Baillie, Malcolm G Semple, Mahdad Noursadeghi, Peter JM Openshaw, Beatrice Alex, Benjamin Bach, Wendy S Barclay, Debby Bogaert, Meera Chand, Graham S Cooke, Ana da Silva Filipe, Tom Fletcher, Julian A Hiscox, Antonia Ying Wai Ho, Samreen Ijaz, Saye Khoo, Paul Klenerman, Andrew Law, Wei Shen Lim, Alexander J Mentzer, Alison M Meynert, Shona C Moore, Massimo Palmarini, William A Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L Robertson, Vanessa Sancho-Shimizu, Janet T Scott, Thushan de Silva, Louise Sigfrid, Shiranee Sriskandan, David Stuart, Charlotte Summers, Richard S Tedder, Emma C Thomson, AA Roger Thompson, Ryan S Thwaites, Lance CW Turtle, Maria Zambon, Hayley Hardwick, Chloe Donohue, Ruth Lyons, Fiona Griffiths, Wilna Oosthuyzen, Tom M Drake, Stephen Knight, Derek Murphy, Jo Dalton, James Lee, Daniel Plotkin, Michelle Girvan, Scott Mullaney, Claire Petersen, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Gary Leeming, Murray Wham, Sara Clohisey, Ross Hendry, William Greenhalf, Victoria Shaw, Sarah McDonald, Seán Keating, Katie A. Ahmed, Jane A Armstrong, Milton Ashworth, Innocent G Asiimwe, Siddharth Bakshi, Samantha L Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Benjamin WA Catterall, Jordan J Clark, Emily A Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis WS Fisher, Terry Foster, Isabel Garcia-Dorival, Willliam Greenhalf, Philip Gunning, Catherine Hartley, Rebecca L Jensen, Christopher B Jones, Trevor R Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, L Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A Livoti, Maria Mancini, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S Miah, Joanna Middleton, Joyce Mitchell, Ellen G Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E Shaw, Rebecca K Shears, Benjamin Small, Krishanthi S Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Ana Alegria, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Nicola Best, Pieter Bothma, David Brealey, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, David Chadwick, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic, Phil Donnison, Sam Douthwaite, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Clive Graham, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Mariyam Mirfenderesky, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Igor Otahal, Mark Pais, Selva Panchatsharam, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Brendan Ryan, Taranprit Saluja, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Andrew Ustianowski, Nick Vallotton, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Sarah Wilson, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G Wooton, Andrew Workman, Bryan Yates, Peter Young, National Institute for Health Research, Commission of the European Communities, Medical Research Council (MRC), UKRI MRC COVID-19 Rapid Response Call, UK Research and Innovation, Gupta, Rishi K [0000-0002-6257-1285], Lipman, Marc [0000-0001-7501-4448], Buchan, Iain [0000-0003-3392-1650], and Apollo - University of Cambridge Repository
Subjects: Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Critical Care, Clinical Decision-Making, MEDLINE, Logistic regression, ResearchInstitutes_Networks_Beacons/humanitarian_conflict_response_institute, Severity of Illness Index, 1117 Public Health and Health Services, 03 medical and health sciences, 0302 clinical medicine, Patient Admission, Clinical Decision Rules, Severity of illness, Medicine, Humans, 030212 general & internal medicine, Hospital Mortality, Prospective Studies, Prospective cohort study, ISARIC4C Investigators, Aged, Aged, 80 and over, Clinical Deterioration, business.industry, SARS-CoV-2, Reproducibility of Results, COVID-19, 1103 Clinical Sciences, Articles, Middle Aged, Medical research, Prognosis, Respiration, Artificial, United Kingdom, Intensive Care Units, Logistic Models, 030228 respiratory system, Preparedness, Emergency medicine, Cohort, Humanitarian and Conflict Response Institute, Female, business, 1199 Other Medical and Health Sciences
Abstract: Background\ud \ud Prognostic models to predict the risk of clinical deterioration in acute COVID-19 cases are urgently required to inform clinical management decisions.\ud \ud \ud Methods\ud \ud We developed and validated a multivariable logistic regression model for in-hospital clinical deterioration (defined as any requirement of ventilatory support or critical care, or death) among consecutively hospitalised adults with highly suspected or confirmed COVID-19 who were prospectively recruited to the International Severe Acute Respiratory and Emerging Infections Consortium Coronavirus Clinical Characterisation Consortium (ISARIC4C) study across 260 hospitals in England, Scotland, and Wales. Candidate predictors that were specified a priori were considered for inclusion in the model on the basis of previous prognostic scores and emerging literature describing routinely measured biomarkers associated with COVID-19 prognosis. We used internal–external cross-validation to evaluate discrimination, calibration, and clinical utility across eight National Health Service (NHS) regions in the development cohort. We further validated the final model in held-out data from an additional NHS region (London).\ud \ud \ud Findings\ud \ud 74 944 participants (recruited between Feb 6 and Aug 26, 2020) were included, of whom 31 924 (43·2%) of 73 948 with available outcomes met the composite clinical deterioration outcome. In internal–external cross-validation in the development cohort of 66 705 participants, the selected model (comprising 11 predictors routinely measured at the point of hospital admission) showed consistent discrimination, calibration, and clinical utility across all eight NHS regions. In held-out data from London (n=8239), the model showed a similarly consistent performance (C-statistic 0·77 [95% CI 0·76 to 0·78]; calibration-in-the-large 0·00 [–0·05 to 0·05]); calibration slope 0·96 [0·91 to 1·01]), and greater net benefit than any other reproducible prognostic model.\ud \ud \ud Interpretation\ud \ud The 4C Deterioration model has strong potential for clinical utility and generalisability to predict clinical deterioration and inform decision making among adults hospitalised with COVID-19.\ud \ud \ud Funding\ud \ud National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, Department for International Development, Bill & Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, NIHR HPRU in Respiratory Infections at Imperial College London.
Published: 2021
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14. Individualized Hemodynamic Management in Sepsis

Author: Máté Rottler, Marcell Virág, Zsolt Molnár, Tamas Leiner, and Klementina Ocskay
Subjects: Resuscitation, medicine.medical_specialty, early goal-directed therapy, media_common.quotation_subject, Population, Medicine (miscellaneous), lcsh:Medicine, Review, Early goal-directed therapy, hemodynamic monitoring, Neglect, Sepsis, fluid therapy, 03 medical and health sciences, 0302 clinical medicine, Intensive care, medicine, 030212 general & internal medicine, Intensive care medicine, education, media_common, education.field_of_study, lactate, Septic shock, business.industry, lcsh:R, 030208 emergency & critical care medicine, medicine.disease, Regimen, septic shock, business
Abstract: Hemodynamic optimization remains the cornerstone of resuscitation in the treatment of sepsis and septic shock. Delay or inadequate management will inevitably lead to hypoperfusion, tissue hypoxia or edema, and fluid overload, leading eventually to multiple organ failure, seriously affecting outcomes. According to a large international survey (FENICE study), physicians frequently use inadequate indices to guide fluid management in intensive care units. Goal-directed and “restrictive” infusion strategies have been recommended by guidelines over “liberal” approaches for several years. Unfortunately, these “fixed regimen” treatment protocols neglect the patient’s individual needs, and what is shown to be beneficial for a given population may not be so for the individual patient. However, applying multimodal, contextualized, and personalized management could potentially overcome this problem. The aim of this review was to give an insight into the pathophysiological rationale and clinical application of this relatively new approach in the hemodynamic management of septic patients.
Published: 2021

15. Clinical characteristics of children and young people admitted to hospital with covid-19 in United Kingdom: prospective multicentre observational cohort study

Author: Alexander Mentzer, Louisa Pollock, David Brealey, Mahdad Noursadeghi, Charlotte Summers, Graciela Isabel García Dorival, Mark Pritchard, Andrew Ustianowski, Ryan Thwaites, Quen Mok, Innocent Gerald Asiimwe, Stuart Hartshorn, Lance Turtle, Lauren Lett, Shondipon Laha, Malcolm Gracie Semple, Tom Fletcher, Chrysa Koukorava, Patrick Lillie, Ewen Harrison, Suzannah Lant, Louise Sigfrid, Meera Chand, Chloe Donohue, Ahilanandan Dushianthan, Jordan Clark, Christopher Green, Mark Peters, Sarah McDonald, Paul Dark, Luke Hodgson, Emma Thomson, Tamas Leiner, William Paxton, Georgios Pollakis, Shona Moore, Janet Scott, John Kenneth Baillie, Semple, Malcolm G [0000-0001-9700-0418], Apollo - University of Cambridge Repository, Baillie, JK, Semple, MG, Openshaw, PJM, Alex, B, Bach, B, Barclay, WS, Bogaert, D, Chand, M, Cooke, GS, Docherty, AB, Dunning, J, Da Silva Filipe, A, Fletcher, T, Green, CA, Harrison, EM, Hiscox, JA, Ying Wai Ho, A, Horby, PW, Ijaz, S, Khoo, S, Klenerman, P, Law, A, Lim, WS, Mentzer, AJ, Merson, L, Meynert, AM, Noursadeghi, M, Moore, SC, Palmarini, M, Paxton, WA, Pollakis, G, Price, N, Rambaut, A, Robertson, DL, Russell, CD, Sancho-Shimizu, V, Scott, JT, Sigfrid, L, Solomon, T, Sriskandan, S, Stuart, D, Summers, C, Tedder, RS, Thomson, EC, Thwaites, RS, Turtle, LCW, Zambon, M, Hardwick, H, Donohue, C, Ewins, J, Oosthuyzen, W, Griffiths, F, Norman, L, Pius, R, Drake, TM, Fairfield, CJ, Knight, S, Mclean, KA, Murphy, D, Shaw, CA, Dalton, J, Girvan, M, Saviciute, E, Roberts, S, Harrison, J, Marsh, L, Connor, M, Halpin, S, Jackson, C, Gamble, C, Leeming, G, Hendry, R, Greenhalf, W, Shaw, V, McDonald, S, Ahmed, KA, Armstrong, JA, Ashworth, M, Asiimwe, IG, Bakshi, S, Barlow, SL, Booth, L, Brennan, B, Bullock, K, Catterall, BWA, Clark, JJ, Clarke, EA, Cole, S, Cooper, L, Cox, H, Davis, C, Dincarslan, O, Dunn, C, Dyer, P, Elliott, A, Evans, A, Fisher, LWS, Foster, T, Garcia-Dorival, I, Gunning, P, Hartley, C, Ho, A, Jensen, RL, Jones, CB, Jones, TR, Khandaker, S, King, K, Kiy, RT, Koukorava, C, Lake, A, Lant, S, Latawiec, D, Lavelle-Langham, L, Lefteri, D, Lett, L, Livoti, LA, Mancini, M, McEvoy, L, McLauchlan, J, Metelmann, S, Miah, NS, Middleton, J, Mitchell, J, Murphy, EG, Penrice-Randal, R, Pilgrim, J, Prince, T, Reynolds, W, Ridley, PM, Sales, D, Shaw, VE, Shears, RK, Small, B, Subramaniam, KS, Szemiel, A, Taggart, A, Tanianis, J, Thomas, J, Trochu, E, Van Tonder, L, Wilcock, E, Zhang, JE, Adeniji, K, Agranoff, D, Agwuh, K, Ail, D, Alegria, A, Angus, B, Ashish, A, Atkinson, D, Bari, S, Barlow, G, Barnass, S, Barrett, N, Bassford, C, Baxter, D, Beadsworth, M, Bernatoniene, J, Berridge, J, Best, N, Bothma, P, Brealey, D, Brittain-Long, R, Bulteel, N, Burden, T, Burtenshaw, A, Caruth, V, Chadwick, D, Chambler, D, Chee, N, Child, J, Chukkambotla, S, Clark, T, Collini, P, Cosgrove, C, Cupitt, J, Cutino-Moguel, M-T, Dark, P, Dawson, C, Dervisevic, S, Donnison, P, Douthwaite, S, DuRand, I, Dushianthan, A, Dyer, T, Evans, C, Eziefula, C, Fegan, C, Finn, A, Fullerton, D, Garg, S, Garg, A, Godden, J, Goldsmith, A, Graham, C, Hardy, E, Hartshorn, S, Harvey, D, Havalda, P, Hawcutt, DB, Hobrok, M, Hodgson, L, Holme, A, Hormis, A, Jacobs, M, Jain, S, Jennings, P, Kaliappan, A, Kasipandian, V, Kegg, S, Kelsey, M, Kendall, J, Kerrison, C, Kerslake, I, Koch, O, Koduri, G, Koshy, G, Laha, S, Larkin, S, Leiner, T, Lillie, P, Limb, J, Linnett, V, Little, J, MacMahon, M, MacNaughton, E, Mankregod, R, Masson, H, Matovu, E, McCullough, K, McEwen, R, Meda, M, Mills, G, Minton, J, Mirfenderesky, M, Mohandas, K, Mok, Q, Moon, J, Moore, E, Morgan, P, Morris, C, Mortimore, K, Moses, S, Mpenge, M, Mulla, R, Murphy, M, Nagel, M, Nagarajan, T, Nelson, M, Otahal, I, Pais, M, Panchatsharam, S, Paraiso, H, Patel, B, Pepperell, J, Peters, M, Phull, M, Pintus, S, Pooni, JS, Post, F, Price, D, Prout, R, Rae, N, Reschreiter, H, Reynolds, T, Richardson, N, Roberts, M, Roberts, D, Rose, A, Rousseau, G, Ryan, B, Saluja, T, Shah, A, Shanmuga, P, Sharma, A, Shawcross, A, Sizer, J, Smith, R, Snelson, C, Spittle, N, Staines, N, Stambach, T, Stewart, R, Subudhi, P, Szakmany, T, Tatham, K, Thompson, C, Thompson, R, Tridente, A, Tupper-Carey, D, Twagira, M, Ustianowski, A, Vallotton, N, Vincent-Smith, L, Visuvanathan, S, Vuylsteke, A, Waddy, S, Wake, R, Walden, A, Welters, I, Whitehouse, T, Whittaker, P, Whittington, A, Wijesinghe, M, Williams, M, Wilson, L, Wilson, S, Winchester, S, Wiselka, M, Wolverson, A, Wooton, DG, Workman, A, Yates, B, and Young, P
Subjects: Male, Pediatrics, Cohort Studies, 0302 clinical medicine, Interquartile range, Medicine, 030212 general & internal medicine, Hospital Mortality, Young adult, Child, Age Factors, General Medicine, Systemic Inflammatory Response Syndrome, Hospitalization, Child, Preschool, Female, Coronavirus Infections, Life Sciences & Biomedicine, Cohort study, medicine.medical_specialty, Adolescent, Critical Care, Pneumonia, Viral, Disease cluster, 1117 Public Health and Health Services, 03 medical and health sciences, Betacoronavirus, Young Adult, Medicine, General & Internal, AGE, General & Internal Medicine, 030225 pediatrics, Intensive care, Humans, ISARIC4C Investigators, Pandemics, Science & Technology, business.industry, SARS-CoV-2, Research, Infant, Newborn, COVID-19, Infant, 1103 Clinical Sciences, Odds ratio, medicine.disease, Comorbidity, Respiration, Artificial, United Kingdom, Systemic inflammatory response syndrome, business
Abstract: Objective To characterise the clinical features of children and young people admitted to hospital with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK and explore factors associated with admission to critical care, mortality, and development of multisystem inflammatory syndrome in children and adolescents temporarily related to coronavirus disease 2019 (covid-19) (MIS-C). Design Prospective observational cohort study with rapid data gathering and near real time analysis. Setting 260 hospitals in England, Wales, and Scotland between 17 January and 3 July 2020, with a minimum follow-up time of two weeks (to 17 July 2020). Participants 651 children and young people aged less than 19 years admitted to 138 hospitals and enrolled into the International Severe Acute Respiratory and emergency Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK study with laboratory confirmed SARS-CoV-2. Main outcome measures Admission to critical care (high dependency or intensive care), in-hospital mortality, or meeting the WHO preliminary case definition for MIS-C. Results Median age was 4.6 (interquartile range 0.3-13.7) years, 35% (225/651) were under 12 months old, and 56% (367/650) were male. 57% (330/576) were white, 12% (67/576) South Asian, and 10% (56/576) black. 42% (276/651) had at least one recorded comorbidity. A systemic mucocutaneous-enteric cluster of symptoms was identified, which encompassed the symptoms for the WHO MIS-C criteria. 18% (116/632) of children were admitted to critical care. On multivariable analysis, this was associated with age under 1 month (odds ratio 3.21, 95% confidence interval 1.36 to 7.66; P=0.008), age 10-14 years (3.23, 1.55 to 6.99; P=0.002), and black ethnicity (2.82, 1.41 to 5.57; P=0.003). Six (1%) of 627 patients died in hospital, all of whom had profound comorbidity. 11% (52/456) met the WHO MIS-C criteria, with the first patient developing symptoms in mid-March. Children meeting MIS-C criteria were older (median age 10.7 (8.3-14.1) v 1.6 (0.2-12.9) years; Pv 42% (148/355); P=0.004). Children with MIS-C were five times more likely to be admitted to critical care (73% (38/52) v 15% (62/404); Pv 28% (86/302); P=0.004), headache (34% (16/47) v 10% (26/263); Pv 8% (21/270); Pv (12% (34/284); P=0.003), and lymphadenopathy (20% (9/46) v 3% (10/318); P9 /L (32% (16/50) v 11% (38/348); P Conclusions Children and young people have less severe acute covid-19 than adults. A systemic mucocutaneous-enteric symptom cluster was also identified in acute cases that shares features with MIS-C. This study provides additional evidence for refining the WHO MIS-C preliminary case definition. Children meeting the MIS-C criteria have different demographic and clinical features depending on whether they have acute SARS-CoV-2 infection (polymerase chain reaction positive) or are post-acute (antibody positive). Study registration ISRCTN66726260.
Published: 2021
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16. Outcome of Hospitalization for COVID-19 in Patients with Interstitial Lung Disease. An International Multicenter Study

Author: Thomas M. Drake, Annemarie B. Docherty, Ewen M. Harrison, Jennifer K. Quint, Huzaifa Adamali, Sarah Agnew, Suresh Babu, Christopher M. Barber, Shaney Barratt, Elisabeth Bendstrup, Stephen Bianchi, Diego Castillo Villegas, Nazia Chaudhuri, Felix Chua, Robina Coker, William Chang, Anjali Crawshaw, Louise E. Crowley, Davinder Dosanjh, Christine A. Fiddler, Ian A. Forrest, Peter M. George, Michael A. Gibbons, Katherine Groom, Sarah Haney, Simon P. Hart, Emily Heiden, Michael Henry, Ling-Pei Ho, Rachel K. Hoyles, John Hutchinson, Killian Hurley, Mark Jones, Steve Jones, Maria Kokosi, Michael Kreuter, Laura S. MacKay, Siva Mahendran, George Margaritopoulos, Maria Molina-Molina, Philip L. Molyneaux, Aiden O’Brien, Katherine O’Reilly, Alice Packham, Helen Parfrey, Venerino Poletti, Joanna C. Porter, Elisabetta Renzoni, Pilar Rivera-Ortega, Anne-Marie Russell, Gauri Saini, Lisa G. Spencer, Giulia M. Stella, Helen Stone, Sharon Sturney, David Thickett, Muhunthan Thillai, Tim Wallis, Katie Ward, Athol U. Wells, Alex West, Melissa Wickremasinghe, Felix Woodhead, Glenn Hearson, Lucy Howard, J. Kenneth Baillie, Peter J. M. Openshaw, Malcolm G. Semple, Iain Stewart, R. Gisli Jenkins, Gail Carson, Beatrice Alex, Benjamin Bach, Wendy S. Barclay, Debby Bogaert, Meera Chand, Graham S. Cooke, Jake Dunning, Ana da Silva Filipe, Tom Fletcher, Christopher A. Green, Julian A. Hiscox, Antonia Ying Wai Ho, Peter W. Horby, Samreen Ijaz, Saye Khoo, Paul Klenerman, Andrew Law, Wei Shen Lim, Alexander J. Mentzer, Laura Merson, Alison M. Meynert, Mahdad Noursadeghi, Shona C Moore, Massimo Palmarini, William A Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L Robertson, Clark D. Russell, Vanessa Sancho-Shimizu, Janet T. Scott, Thushan de Silva, Louise Sigfrid, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Richard S. Tedder, Emma C. Thomson, A. A. Roger Thompson, Ryan S. Thwaites, Lance C. W. Turtle, Maria Zambon, Hayley Hardwick, Chloe Donohue, Ruth Lyons, Fiona Griffiths, Wilna Oosthuyzen, Lisa Norman, Riinu Pius, Tom M. Drake, Cameron J. Fairfield, Stephen Knight, Kenneth A. Mclean, Derek Murphy, Catherine A. Shaw, Jo Dalton, Michelle Girvan, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Sophie Halpin, Clare Jackson, Carrol Gamble, Gary Leeming, Murray Wham, Sara Clohisey, Ross Hendry, James Scott-Brown, William Greenhalf, Victoria Shaw, Sarah McDonald, Seán Keating, Katie A. Ahmed, Jane A. Armstrong, Milton Ashworth, Innocent G. Asiimwe, Siddharth Bakshi, Samantha L. Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Benjamin W. A. Catterall, Jordan J. Clark, Emily A. Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis W. S. Fisher, Terry Foster, Isabel Garcia-Dorival, Willliam Greenhalf, Philip Gunning, Catherine Hartley, Antonia Ho, Rebecca L. Jensen, Christopher B. Jones, Trevor R. Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, L. Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A. Livoti, Maria Mancini, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S. Miah, Joanna Middleton, Joyce Mitchell, Shona C. Moore, Ellen G. Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E. Shaw, Rebecca K. Shears, Benjamin Small, Krishanthi S. Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Ana Alegria, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Nicola Best, Pieter Bothma, David Brealey, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, David Chadwick, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic, Phil Donnison, Sam Douthwaite, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Clive Graham, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B. Hawcutt, Maria Hobrok, Luke Hodgson, Anita Holme, Anil Hormis, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Mariyam Mirfenderesky, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Igor Otahal, Mark Pais, Selva Panchatsharam, Hassan Paraiso, Brij Patel, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Brendan Ryan, Taranprit Saluja, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Andrew Ustianowski, Nick Vallotton, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Sarah Wilson, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G. Wooton, Andrew Workman, Bryan Yates, Peter Young, Thickett, David [0000-0002-5456-6080], Baillie, J Kenneth [0000-0001-5258-793X], Openshaw, Peter JM [0000-0002-7220-2555], Apollo - University of Cambridge Repository, Action for Pulmonary Fibrosis, National Institute for Health Research, and UK Research and Innovation
Subjects: Male, obesity, Respiratory System, Comorbidity, ResearchInstitutes_Networks_Beacons/humanitarian_conflict_response_institute, Critical Care and Intensive Care Medicine, Idiopathic pulmonary fibrosis, 0302 clinical medicine, 030212 general & internal medicine, Lung, License, 11 Medical and Health Sciences, interstitial lung disease, Aged, 80 and over, Interstitial lung disease, respiratory system, Middle Aged, COVID-19, IPF, ILD, Obesity, Lung Function, hospitalisation, idiopathic pulmonary fibrosis, Europe, Hospitalization, COVID-19/Interstitial Lung Disease, ACUTE EXACERBATION, Humanitarian and Conflict Response Institute, Disease Progression, Female, Life Sciences & Biomedicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), behavioral disciplines and activities, 03 medical and health sciences, Critical Care Medicine, General & Internal Medicine, medicine, Humans, In patient, Obesity, ISARIC4C Investigators, Aged, Retrospective Studies, Science & Technology, business.industry, SARS-CoV-2, COVID-19, Retrospective cohort study, lung function, Original Articles, medicine.disease, Lung function, respiratory tract diseases, Clinical trial, body regions, 030228 respiratory system, Case-Control Studies, Emergency medicine, IDIOPATHIC PULMONARY-FIBROSIS, business, Lung Diseases, Interstitial, Tomography, X-Ray Computed
Abstract: Rationale: The impact of coronavirus disease (COVID-19) on patients with interstitial lung disease (ILD) has not been established. Objectives: To assess outcomes in patients with ILD hospitalized for COVID-19 versus those without ILD in a contemporaneous age-, sex-, and comorbidity-matched population. Methods: An international multicenter audit of patients with a prior diagnosis of ILD admitted to the hospital with COVID-19 between March 1 and May 1, 2020, was undertaken and compared with patients without ILD, obtained from the ISARIC4C (International Severe Acute Respiratory and Emerging Infection Consortium Coronavirus Clinical Characterisation Consortium) cohort, admitted with COVID-19 over the same period. The primary outcome was survival. Secondary analysis distinguished idiopathic pulmonary fibrosis from non–idiopathic pulmonary fibrosis ILD and used lung function to determine the greatest risks of death. Measurements and Main Results: Data from 349 patients with ILD across Europe were included, of whom 161 were admitted to the hospital with laboratory or clinical evidence of COVID-19 and eligible for propensity score matching. Overall mortality was 49% (79/161) in patients with ILD with COVID-19. After matching, patients with ILD with COVID-19 had significantly poorer survival (hazard ratio [HR], 1.60; confidence interval, 1.17–2.18; P = 0.003) than age-, sex-, and comorbidity-matched controls without ILD. Patients with an FVC of Conclusions: Patients with ILD are at increased risk of death from COVID-19, particularly those with poor lung function and obesity. Stringent precautions should be taken to avoid COVID-19 in patients with ILD.
Published: 2020
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17. Avoiding perioperative oxygen debt

Author: Krisztian Tanczos, Tamas Leiner, and Zsolt Molnár
Subjects: Cardiac output, medicine.medical_specialty, Perioperative management, business.industry, Hemodynamics, Perioperative, Critical Care and Intensive Care Medicine, Oxygen debt, Blood pressure, Shock (circulatory), Emergency Medicine, medicine, medicine.symptom, Intensive care medicine, business, Urine output
Abstract: Perioperative management of high-risk surgical patients is a complex and complicated process. Hemodynamic instability can inflict vital organ hypoperfusion that can have several serious consequences, mainly due to cellular oxygen debt. Therefore, adequate monitoring guided early interventions are inevitable to avoid serious postoperative complications. However, conventional indices, including heart rate, blood pressure, skin temperature and urine output have limited value in diagnosing compensated shock. Therefore, advanced hemodynamic monitoring may become necessary when in addition to cardiac output other measures of oxygen delivery are also taken into account during treatment. However, any alteration that aims to affect macrocirculation only makes sense if it is followed by improved microcirculatory perfusion and adequate oxygen delivery to the cells. Putting the puzzle of hemodynamic stabilization together requires a complex, holistic approach. The purpose of this review is to discuss the holistic approach of multimodal, individualized monitoring that can help to avoid perioperative oxygen debt in high risk surgical patients.
Published: 2020
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18. Effects of IgM-Enriched Immunoglobulin Therapy in Septic-Shock–Induced Multiple Organ Failure: Pilot Study

Author: A Mikor, Ildikó Y. Tóth, Zsolt Molnár, Tamas Szakmany, Tamas Leiner, and Lajos Bogár
Subjects: Male, Multiple Organ Failure, medicine.medical_treatment, Pilot Projects, Procalcitonin, Sepsis, Organ Dysfunction Scores, medicine, Humans, Prospective Studies, Aged, Mechanical ventilation, biology, business.industry, Septic shock, C-reactive protein, Organ dysfunction, Middle Aged, medicine.disease, Shock, Septic, Anesthesiology and Pain Medicine, Immunoglobulin M, Respiratory failure, Anesthesia, biology.protein, Female, medicine.symptom, business
Abstract: Mortality due to septic-shock-induced respiratory failure remains high. A recent meta-analysis suggested that IgM-enriched immunoglobulin treatment may be beneficial in these patients. In this prospective randomised controlled pilot study we investigated the effects of IgM-enriched immunoglobulin treatment in patients with early septic shock accompanied by severe respiratory failure. 33 patients were randomly allocated to receive 5 ml/kg (predicted body weight) IgM-enriched immunoglobulin (16 patients) or placebo (17 patients), respectively, via 8 h IV-infusion for three consecutive days. Daily Multiple Organ Dysfunction Scores (MODS) were calculated. Serum C-reactive protein (CRP) and procalcitonin (PCT) levels were monitored daily. For statistical analysis two-way ANOVA was used. Daily MODS showed ongoing multiple system organ failure without significant resolution during the 8 days. Median length of ICU stay, mechanical ventilation, vasopressor support during the ICU stay and 28-day mortality were nearly identical in the two groups. Serum PCT levels showed no significant difference between the two groups, however, CRP levels were significantly lower in the IgM-enriched immunoglobulin group on days 4, 5 and 6, respectively. In this study the use of IgM-enriched immunoglobulin preparation failed to produce any improvement in the organ dysfunction as compared to standard sepsis therapy.
Published: 2013
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19. Hemodynamic and respiratory changes during lung recruitment and descending optimal positive end-expiratory pressure titration in patients with acute respiratory distress syndrome*

Author: A Mikor, Zsolt Molnár, Ildikó Y. Tóth, Tamas Szakmany, Lajos Bogár, and Tamas Leiner
Subjects: Adult, Male, Pulmonary Atelectasis, Resuscitation, Central Venous Pressure, Hemodynamics, Blood Pressure, Critical Care and Intensive Care Medicine, law.invention, Hospitals, University, Positive-Pressure Respiration, Heart Rate, law, Intensive care, Tidal Volume, medicine, Humans, Cardiac Output, Respiratory system, Lung, Positive end-expiratory pressure, Aged, Air Pressure, Respiratory Distress Syndrome, Blood Volume, Respiratory distress, business.industry, Respiratory disease, Stroke Volume, Middle Aged, medicine.disease, Intensive care unit, Oxygen, Pulmonary Alveoli, Anesthesia, Extravascular Lung Water, Female, Pulmonary Ventilation, business
Abstract: To investigate respiratory and hemodynamic changes during lung recruitment and descending optimal positive end-expiratory pressure (PEEP) titration.Prospective auto-control clinical trial.Adult general intensive care unit in a university hospital.Eighteen patients with acute respiratory distress syndrome.Following baseline measurements (T0), PEEP was set at 26 cm H2O and lung recruitment was performed (40/40-maneuver). Then tidal volume was set at 4 mL/kg (T26R) and PEEP was lowered by 2 cm H2O in every 4 mins. Optimal PEEP was defined at 2 cm H2O above the PEEP where Pao2 dropped by10%. After setting the optimal PEEP, the 40/40-maneuver was repeated and tidal volume set at 6 mL/kg (T(end)).Arterial blood gas analysis was done every 4 mins and hemodynamic measurements every 8 mins until T(end), then in 30 (T30) and 60 (T60) mins. The Pao2 increased from T0 to T(end) (203 +/- 108 vs. 322 +/- 101 mm Hg, p.001), but the extravascular lung water (EVLW) did not change significantly. Cardiac index (CI) and the intrathoracic blood volume (ITBV) decreased from T0 to T26R (CI, 3.90 +/- 1.04 vs. 3.62 +/- 0.91 L/min/m2, p.05; ITBVI, 832 +/- 205 vs. 795 +/- 188 m/m2, p.05). There was a positive correlation between CI and ITBVI (r = .699, p.01), a negative correlation between CI and central venous pressure (r = -.294, p.01), and no correlation between CI and mean arterial pressure (MAP).Following lung recruitment and descending optimal PEEP titration, the Pao2 improves significantly, without any change in the EVLW up to 1 hr. This suggests a decrease in atelectasis as a result of recruitment rather than a reduction of EVLW. There is a significant change in CI during the maneuver, but neither central venous pressure, heart rate, nor MAP can reflect these changes.
Published: 2007
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20. Clinical Frailty Scale (CFS) indicated frailty is associated with increased in-hospital and 30-day mortality in COVID-19 patients: a systematic review and meta-analysis

Author: Máté Rottler, Klementina Ocskay, Zoltán Sipos, Anikó Görbe, Marcell Virág, Péter Hegyi, Tihamér Molnár, Bálint Erőss, Tamás Leiner, and Zsolt Molnár
Subjects: Intensive care, Clinical Frailty Scale, Hospital Frailty Risk Score, Ceiling of care, Geriatric, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background The concept of frailty provides an age-independent, easy-to-use tool for risk stratification. We aimed to summarize the evidence on the efficacy of frailty tools in risk assessment in COVID-19 patients. Methods The protocol was registered (CRD42021241544). Studies reporting on frailty in COVID-19 patients were eligible. The main outcomes were mortality, length of hospital stay (LOH) and intensive care unit (ICU) admission in frail and non-frail COVID-19 patients. Frailty was also compared in survivors and non-survivors. Five databases were searched up to 24th September 2021. The QUIPS tool was used for the risk of bias assessment. Odds ratios (OR) and weighted mean differences (WMD) were calculated with 95% confidence intervals (CI) using a random effect model. Heterogeneity was assessed using the I 2 and χ 2 tests. Results From 3640 records identified, 54 were included in the qualitative and 42 in the quantitative synthesis. Clinical Frailty Scale (CFS) was used in 46 studies, the Hospital Frailty Risk Score (HFRS) by 4, the Multidimensional Prognostic Index (MPI) by 3 and three studies used other scores. We found that patients with frailty (CFS 4–9 or HFRS ≥ 5) have a higher risk of mortality (CFS: OR: 3.12; CI 2.56–3.81; HFRS OR: 1.98; CI 1.89–2.07). Patients with frailty (CFS 4–9) were less likely to be admitted to ICU (OR 0.28, CI 0.12–0.64). Quantitative synthesis for LOH was not feasible. Most studies carried a high risk of bias. Conclusions As determined by CFS, frailty is strongly associated with mortality; hence, frailty-based patient management should be included in international COVID-19 treatment guidelines. Future studies investigating the role of frailty assessment on deciding ICU admission are strongly warranted.
Published: 2022
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21. Plasma somatostatin-like immunoreactivity increases in the plasma of septic patients and rats with systemic inflammatory reaction: experimental evidence for its sensory origin and protective role

Author: Krisztian Tanczos, János Szolcsányi, Zsuzsanna Helyes, Tamas Leiner, Teréz Bagoly, Timea Nemeth, Csaba Loibl, István Szitter, Bianka Varnai, Erika Pintér, Zsofia Bardonicsek, Tihamer Molnar, and Balazs Suto
Subjects: Male, medicine.medical_specialty, Sensory Receptor Cells, Physiology, CD40 Ligand, Resiniferatoxin, Vascular Cell Adhesion Molecule-1, Lung injury, Biochemistry, Cellular and Molecular Neuroscience, Cecum, chemistry.chemical_compound, Endocrinology, Internal medicine, Sepsis, medicine, Animals, Humans, Interleukin 8, Rats, Wistar, Interleukin 6, Aged, biology, Somatostatin receptor, business.industry, Interleukin-6, Middle Aged, medicine.disease, Systemic Inflammatory Response Syndrome, Systemic inflammatory response syndrome, Disease Models, Animal, P-Selectin, medicine.anatomical_structure, Somatostatin, chemistry, biology.protein, Cytokines, Female, Capsaicin, business, Peptides, Biomarkers
Abstract: Alterations of somatostatin-like immunoreactivity (SST-LI) in the plasma of 11 systemic inflammatory response syndrome (SIRS) patients were investigated in correlation with cytokines, adhesion molecules and coagulation markers repeatedly during 4 days. The origin and role of SST were studied in the cecum ligation and puncture (CLP) rat SIRS model. Capsaicin-sensitive peptidergic sensory nerves were defunctionalized by resiniferatoxin (RTX) pretreatment 2 weeks earlier, in a separate group animals were treated with the somatostatin receptor antagonist cyclo-somatostatin (C-SOM). Plasma SST-LI significantly elevated in septic patients compared to healthy volunteers during the whole 4-day period. Significantly decreased Horowitz score showed severe lung injury, increased plasma C-reactive protein and procalcitonin confirmed SIRS. Soluble P-selectin, tissue plasminogen activator and the interleukin 8 and monocyte chemotactic protein-1 significantly increased, interleukin 6 and soluble CD40 ligand did not change, and soluble Vascular Adhesion Molecule-1 decreased. SST-LI significantly increased in rats both in the plasma and the lung 6 h after CLP compared to sham-operation. After RTX pretreatment SST-LI was not altered in intact animals, but the SIRS-induced elevation was absent. Lung MPO activity significantly increased 6 h following CLP compared to sham operation, which was significantly higher both after RTX-desensitization and C-SOM-treatment. Most non-pretreated operated rats survived the 6 h, but 60% of the RTX-pretreated ones died showing a significantly worse survival. This is the first comprehensive study in humans and animal experiments providing evidence that SST is released from the activated peptidergic sensory nerves. It gets into the bloodstream and mediates a potent endogenous protective mechanism.
Published: 2013

22. Addition of daratumumab to multiple myeloma backbone regimens significantly improves clinical outcomes: a systematic review and meta-analysis of randomised controlled trials

Author: Szabolcs Kiss, Noémi Gede, Péter Hegyi, Bettina Nagy, Rita Deák, Fanni Dembrovszky, Stefania Bunduc, Bálint Erőss, Tamás Leiner, Zsolt Szakács, and Hussain Alizadeh
Subjects: Medicine, Science
Abstract: Abstract Daratumumab has shown clinical benefit in multiple myeloma. We aimed to evaluate the safety and efficacy of adding daratumumab to backbone anti-myeloma treatments. Systematic search was performed up to August 2021 to identify randomised controlled trials comparing the outcomes of backbone therapy with and without daratumumab in relapsed/refractory and newly diagnosed myeloma (RRMM and NDMM, respectively). Odds ratios (ORs) and hazard ratios (HRs) were calculated with 95% confidence intervals (CIs). Primary outcomes were death or disease progression, minimal residual disease (MRD) negativity, and stringent complete response (sCR). Secondary outcomes were complete response or better and safety endpoints prespecified in the study protocol: PROSPERO (CRD42020222904). In NDMM, MRD negativity [OR = 3.61 (CI 2.33–5.61)] and sCR [OR = 2.29 (CI 1.49–3.51)] were more likely and death or disease progression [HR = 0.47 (CI 0.39–0.57)] was less likely to occur with daratumumab compared to control. Regarding RRMM, MRD negativity [OR = 5.43 (CI 2.76–10.66)] and sCR [OR = 3.08 (CI 2.00–4.76)] were more likely and death or disease progression was less likely [HR = 0.50 (CI 0.37–0.67)] with daratumumab compared to control. The addition of daratumumab has shown high clinical efficacy and acceptable toxicity profile for the treatment of NDMM and RRMM regarding the endpoints examined.
Published: 2021
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23. Effect of HO-3089 PARP inhibitor on inflammatory response

Author: Krisztian Tanczos, M. Németh, A Mikor, K Kovacs, Tamas Leiner, and Zsolt Molnár
Subjects: Veterinary medicine, business.industry, Poly ADP ribose polymerase, Inflammatory response, Pharmacology, Critical Care and Intensive Care Medicine, medicine.disease, Systemic inflammation, Pathophysiology, Sepsis, Animal model, Poster Presentation, PARP inhibitor, medicine, medicine.symptom, business
Abstract: The activation of poly-ADP-ribose-polymerase enzyme (PARP) plays an important role in the pathophysiology of sepsis [1]. In previous animal models, lipopolysaccharide-induced systemic inflammatory response was significantly reduced by the inhibition of PARP [2]. The aim of our study was to investigate the effect of PARP inhibition on systemic inflammation in a septic animal model.
Published: 2011
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24. Hungarian perioperative selenium survey in patients with oesophageal cancer

Author: Béla Fülesdi, Tamas Leiner, M. Németh, Ákos Csomós, A Mikor, Tamás Végh, and Zsolt Molnár
Subjects: medicine.medical_specialty, Pediatrics, Critically ill, business.industry, food and beverages, Cancer, chemistry.chemical_element, Perioperative, Orvostudományok, Critical Care and Intensive Care Medicine, medicine.disease, Klinikai orvostudományok, Gastroenterology, chemistry, Selenium deficiency, Internal medicine, Poster Presentation, Cohort, medicine, In patient, business, Selenium
Abstract: Selenium is one of the most investigated trace elements and an important link in the antioxidant system [1]. It is known that selenium levels are lower than normal at the time of admittance to the ICU in critically ill patients [2]. Several cohort surveys highlight the role of selenium deficiency in the carcinogenesis of oesophageal cancer [3]. Mortality and morbidity data after oesophagectomy may vary, but remain considerably high [4].
Published: 2009

25. Effects of volumetric vs. pressure-guided fluid therapy on postoperative inflammatory response: a prospective, randomized clinical trial

Author: Tamas Szakmany, Tamas Leiner, A Mikor, Zsolt Kovacs, Tamas Koszegi, Ildikó Y. Tóth, and Zsolt Molnár
Subjects: Calcitonin, Male, medicine.medical_specialty, Central Venous Pressure, Calcitonin Gene-Related Peptide, Thermodilution, Hemodynamics, Blood volume, Critical Care and Intensive Care Medicine, Procalcitonin, law.invention, Postoperative Complications, Randomized controlled trial, law, Intensive care, Monitoring, Intraoperative, medicine, Humans, Prospective Studies, Protein Precursors, biology, Blood Volume Determination, business.industry, Tumor Necrosis Factor-alpha, C-reactive protein, Central venous pressure, Middle Aged, Systemic Inflammatory Response Syndrome, Surgery, Blood pressure, C-Reactive Protein, Anesthesia, biology.protein, Fluid Therapy, Female, business
Abstract: To compare intrathoracic blood volume (ITBV) guided fluid management and central venous pressure (CVP) guided therapy in ameliorating the progression of early systemic inflammatory response in patients undergoing major surgery.Prospective, randomized clinical trial.Forty patients undergoing major abdominal surgery were randomized into CVP and ITBV groups.In the CVP group the target CVP was 8-12 mmHg while in the ITBV group the goal was to keep the ITBV between 850 and 950 ml/m2 during the operation.Hemodynamic parameters were determined by single arterial thermodilution. Measurements were repeated every 30 min intraoperatively. Serum procalcitonin (PCT) and C-reactive protein (CRP) was monitored preoperatively, on ICU admission, and then daily for 3 days. Serum TNF-alpha levels were measured intraoperatively hourly and then daily for 3 days. There was no significant difference between the two groups regarding hemodynamic parameters at any assessment point. In the overall population changes in the stroke volume index showed a significant correlation with changes in CVP and ITBV. TNF-alpha levels remained in the normal range intraoperatively and during the three postoperative days in both groups. Preoperatively normal PCT and CRP levels increased significantly postoperatively, without significant differences between the groups.ITBV guided fluid therapy did not alter the magnitude of inflammatory response as monitored by serum PCT, CRP, and TNF-alpha in the early postoperative period.
Published: 2004

26. Extracorporeal Cytokine Removal in Critically Ill COVID-19 Patients: A Case Series

Author: Marcell Virág, Máté Rottler, Klementina Ocskay, Tamás Leiner, Balázs Horváth, Daniel Adam Blanco, Alexa Vasquez, László Bucsi, Ágnes Sárkány, and Zsolt Molnár
Subjects: ARDS, cytokine storm, CRRT, COVID-19, hemoadsorption, Cytosorb, Medicine (General), R5-920
Abstract: Introduction: Extracorporeal hemoadsorption (HA) is a potential adjunctive therapy in severe cases of COVID-19 associated pneumonia. In this retrospective study we report data from critically ill patients treated with HA during the first and second wave of the pandemic.Patients and Methods: All patients, who received HA therapy with CytoSorb within the first 96 h of intensive care unit (ICU) admission without hospital-acquired bacterial superinfection, were included. Clinical and laboratory data were collected: on admission, before (TB) and after (TA) HA therapy.Results: Out of the 367 COVID-19 cases, 13 patients were treated with CytoSorb, also requiring mechanical ventilation and renal replacement therapy. All patients were alive at the end of HA, but only 3 survived hospital stay. From TB-TA there was a tendency of decreasing norepinephrine requirement: 193.7 [IQR: 34.8–270.4] to 50.2 [6.5–243.5] ug/kg/day and increasing PaO2/FiO2 ratio 127.8 (95% CI: 96.0–159.6) to 155.0 (115.3–194.6) mmHg but they did not reach statistical significance (p = 0.14 and 0.58, respectively). Treatment related adverse events were not reported.Conclusion: The treatment was well-tolerated, and there was a tendency toward an improvement in vasopressor need and oxygenation during the course of HA. These observations render the need for prospective randomized trials.
Published: 2021
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27. Goal-directed intraoperative fluid management: central venous pressure vs central venous saturation

Author: Tamas Leiner, Krisztian Tanczos, A Mikor, Ildikó Y. Tóth, and Zsolt Molnár
Subjects: medicine.medical_specialty, business.industry, Internal medicine, Cardiology, medicine, Central venous pressure, Fluid management, Critical Care and Intensive Care Medicine, Saturation (chemistry), business
Published: 2009
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28. Relationship between central venous oxygen saturation measured in the inferior and superior vena cava

Author: Zsolt Molnár, Z Heil, Tamas Leiner, and A Mikor
Subjects: medicine.medical_specialty, business.industry, Femoral vein, Critical Care and Intensive Care Medicine, Oxygen debt, Inferior vena cava, Surgery, medicine.vein, Superior vena cava, Intensive care, Internal medicine, Poster Presentation, cardiovascular system, medicine, Cardiology, cardiovascular diseases, Saturation (chemistry), business, Coagulation Disorder
Abstract: Central venous saturation ScvO2 proved a useful alternative to mixed venous saturation, and also a reliable parameter to evaluate the oxygen debt in emergency and intensive care [1-3]. Under special circumstances of anatomical or coagulation disorders, however, canulation of the jugular or subclavian veins are not recommended. In these cases the femoral vein has to be catheterised. The aim of our prospective study was to investigate the relationship between the ScvO2 measured in the superior vena cava (ScvsO2) and in the inferior vena cava (ScviO2).
Published: 2008

29. Influence of the number of nurses on survival in multiple system organ failure

Author: J Sandor, Tamas Leiner, A Mikor, Zsolt Molnár, Ildikó Y. Tóth, and A Roth
Subjects: medicine.medical_specialty, business.industry, health care facilities, manpower, and services, Emergency medicine, Poster Presentation, medicine, Level ii, Level iii, Critical Care and Intensive Care Medicine, business, Human resources
Abstract: Although requirements of human resources in the ICU are well defined (six nurses per bed in level III and four nurses per bed in level II ICUs), these guidelines are not followed in many countries and evidence is also lacking [1]. The aim of this study was to investigate the effect of the number of nurses on the survival in multiple system organ failure (MSOF) on an eight-bed level-III ICU.
Published: 2008

30. Can liver perfusion improve by adding dobutamine to norepinephrine in septic shock?

Author: A Mikor, Ildikó Y. Tóth, Zsolt Molnár, and Tamas Leiner
Subjects: Norepinephrine (medication), medicine.medical_specialty, Liver perfusion, Anesthesiology and Pain Medicine, business.industry, Septic shock, Internal medicine, Cardiology, Medicine, Dobutamine, business, medicine.disease, medicine.drug
Published: 2005
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31. Haemodynamic monitoring during lung recruitment: ScvO2 or CO?

Author: Tamas Leiner, Zsolt Molnár, A Mikor, Ildikó Y. Tóth, and Tamas Szakmany
Subjects: medicine.medical_specialty, Anesthesiology and Pain Medicine, business.industry, Haemodynamic monitoring, Internal medicine, medicine, Cardiology, business, Lung recruitment
Published: 2005
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32. [Untitled]

Author: A Mikor, Tamas Leiner, Tamas Szakmany, Ildikó Y. Tóth, and Zsolt Molnár
Subjects: medicine.medical_specialty, Preload, Text mining, business.industry, medicine, Data mining, Critical Care and Intensive Care Medicine, Intensive care medicine, business, computer.software_genre, computer
Published: 2005
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33. Fluid resuscitation with colloids of different molecular weight in septic shock

Author: Tamas Szakmany, Tamas Leiner, A Mikor, and Zsolt Molnár
Subjects: Adult, Male, medicine.medical_specialty, Resuscitation, Hemodynamics, Hydroxyethyl starch, Lung injury, Critical Care and Intensive Care Medicine, Hydroxyethyl Starch Derivatives, Intensive care, medicine, Humans, In patient, Colloids, Prospective Studies, Respiratory Distress Syndrome, Septic shock, business.industry, Oxygen Inhalation Therapy, Oxygenation, Middle Aged, respiratory system, medicine.disease, Shock, Septic, respiratory tract diseases, Surgery, Molecular Weight, Treatment Outcome, Anesthesia, Extravascular Lung Water, Poster Presentation, Fluid Therapy, Gelatin, Female, business, Gels, medicine.drug
Abstract: The aim of this study was to investigate the short-term effect of fluid resuscitation with 4% modified fluid gelatine (GEL) versus 6% hydroxyethyl starch (HES) on haemodynamics and oxygenation in patients with septic shock and acute lung injury (ALI).Prospective randomised clinical trial.Twenty-bed intensive care unit in a university hospital.Thirty hypovolemic patients (intrathoracic blood volume index, ITBVI850 ml/m(2)) in septic shock with ALI were randomised into HES (mean molecular weight: 200,000 Dalton, degree of substitution 0.6) and GEL (mean molecular weight: 30,000 Dalton) groups (15 patients each).For fluid resuscitation 250 ml/15 min boluses (max. 1,000 ml) were given until the end point of ITBVI900 ml/m(2) was reached. Repeated haemodynamic measurements were done at baseline (t(b)), at the end point (t(ep)) then at 30 min and 60 min after the end point was reached (t(30), t(60)). Cardiac output, stroke volume, extravascular lung water (EVLW), and oxygen delivery was determined at each assessment point. For statistical analysis two-way ANOVA was used.ITBVI, cardiac index, and oxygen delivery index increased significantly at t(ep) and remained elevated for t(30) and t(60), but there was no significant difference between the two groups. The increase in the ITBVI by 100 ml of infusion was similar in both groups (HES: 26+/-19 ml/m(2) vs GEL: 30+/-19 ml/m(2)). EVLW, remained unchanged, and there was no significant difference between the groups (HES, t(b): 8+/-6, t(60): 8+/-6; GEL, t(b): 8+/-3, t(60): 8+/-3 ml/kg). The PaO(2)/FiO(2) did not change significantly over time or between groups (HES, t(b): 207+/-114, t(60): 189+/-78; GEL, t(b): 182+/-85, t(60): 182+/-85 mmHg).The results of this study indicate that both HES and GEL infusions caused similar short-term change in ITBVI in septic shock, without increasing EVLW or worsening oxygenation.
Published: 2004

34. [Untitled]

Author: A Mikor, Tamas Szakmany, Tamas Leiner, and Zsolt Molnár
Subjects: medicine.medical_specialty, Resuscitation, business.industry, Septic shock, medicine, Critical Care and Intensive Care Medicine, Intensive care medicine, business, medicine.disease
Published: 2004
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32. [Untitled]

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34. [Untitled]

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